Descriptor: "MESH: Receptors, Antigen, T-Cell, alpha-beta" - Searchworks@Jio Institute Digital Library Search Results

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45 results on '"MESH: Receptors, Antigen, T-Cell, alpha-beta"'

1. Higher-Order Looping and Nuclear Organization of Tcra Facilitate Targeted RAG Cleavage and Regulated Rearrangement in Recombination Centers

Author: David G. Schatz, Iannis Aifantis, Panagiotis Ntziachristos, Mariann Micsinai, Joy M. H. Wang, Ludovic Deriano, Yuval Kluger, Jeffrey A. Jeddeloh, Elphège P. Nora, Matthew Rodesch, Julie Chaumeil, Yanhong Ji, Jane A. Skok, New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Développement lymphocytaire et Oncogénèse, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Génétique et Biologie du Développement, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Roche NimbleGen Inc., Yale Cancer Center, Yale School of Medicine [New Haven, Connecticut] (YSM), Yale University [New Haven], Howard Hughes Medical Institute (HHMI), This work is supported by the National Institute ofHealth: R01GM086852 (to J.A.S.), R37AI32524 (to D.G.S.), RO1CA133379,RO1CA105129, RO1CA149655, and RO1GM088847 (to I.A.). J.A.S. is aLeukemia & Lymphoma Society (LLS) scholar. J.C. is an Irvington Institute Fellow of the Cancer Research Institute. M.M. was supported by an NSFIGERT 0333389. L.D. was an LLS Fellow. E.P.N. was supported by the FrenchMinistry of Research and the Association pour la Recherche sur le Cancer(France). I.A. is also supported by the Leukemia & Lymphoma Society (TRPgrant), The V Foundation for Cancer Research, and the Dana Foundation.D.G.S. is an Investigator, and I.A. is an Early Career Scientist of the HowardHughes Medical Institute. The authors from Roche NimbleGen, Inc. (M.J.R.and J.A.J.) recognize a competing interest in this publication as employeesof the company., Lassailly-Bondaz, Anne, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), and Yale University School of Medicine
Subjects: Genome instability, MESH: V(D)J Recombination, Ataxia Telangiectasia Mutated Proteins, Inbred C57BL, MESH: Mice, Knockout, Tumor Suppressor Proteins/metabolism, Mice, 0302 clinical medicine, Transcription (biology), Receptors, Recombinase, Medicine and Health Sciences, MESH: Animals, MESH: Ataxia Telangiectasia Mutated Proteins, lcsh:QH301-705.5, DNA-Binding Proteins/genetics/*metabolism, Genetics, MESH: Histones, 0303 health sciences, MESH: Mice, Inbred CBA, MESH: Receptors, Antigen, T-Cell, alpha-beta, biology, MESH: Genomic Instability, V(D)J recombination, Protein-Serine-Threonine Kinases/metabolism, Chromatin, alpha-beta/genetics/*metabolism, Histone, Antigen, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Cell Nucleus, [SDV.IMM] Life Sciences [q-bio]/Immunology, Knockout, Cleavage (embryo), DNA-binding protein, MESH: Genetic Loci, General Biochemistry, Genetics and Molecular Biology, Genomic Instability, MESH: Protein-Serine-Threonine Kinases, 03 medical and health sciences, MESH: Cell Cycle Proteins, MESH: Mice, Inbred C57BL, MESH: Homeodomain Proteins, Homeodomain Proteins/genetics/*metabolism, Animals, MESH: Tumor Suppressor Proteins, MESH: Mice, Alleles, 030304 developmental biology, MESH: DNA Damage, Histones/genetics, Cell Cycle Proteins/metabolism, MESH: Alleles, Inbred CBA, Biology and Life Sciences, T-Cell, lcsh:Biology (General), Genetic Loci, Cell Nucleus/metabolism, biology.protein, 030217 neurology & neurosurgery, MESH: DNA-Binding Proteins, V(D)J Recombination, DNA Damage
Abstract: International audience; V(D)J recombination is essential for generating a diverse array of B and T cell receptors that can recognize and combat foreign antigens. As with any recombination event, tight control is essential to prevent the occurrence of genetic anomalies that drive cellular transformation. One important aspect of regulation is directed targeting of the RAG recombinase. Indeed, RAG accumulates at the 3' end of individual antigen receptor loci poised for rearrangement; however, it is not known whether focal binding is involved in regulating cleavage, and what mechanisms lead to enrichment of RAG in this region. Here, we show that monoallelic looping out of the 3' end of the T cell receptor α (Tcra) locus, coupled with transcription and increased chromatin/nuclear accessibility, is linked to focal RAG binding and ATM-mediated regulation of monoallelic cleavage on looped-out 3' regions. Our data identify higher-order loop formation as a key determinant of directed RAG targeting and the maintenance of genome stability.
Published: 2013
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2. Mucosal-associated invariant T cell–rich congenic mouse strain allows functional evaluation

Author: Lionel Le Bourhis, Olivier Lantz, Yue Cui, Katarzyna Franciszkiewicz, Yvonne K. Mburu, Sylvie Rabot, Alexandra Kachaner, Emmanuel Martin, Claire Soudais, Stanislas Mondot, Virginie Premel, Livine Duban, Jean Jaubert, Molly A. Ingersoll, Jean-Pierre de Villartay, Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Génétique Fonctionnelle de la Souris, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Biopathologie, Institut Curie [Paris], This work was supported by grants from INSERM, Agence Nationale de la Recherche (ANR), DIM Ile de France, Association pour la Recherche sur la Sclérose En Plaques (ARSEP), Institut Mérieux, and Institut Curie. Y.K. Mburu is a recipient of the Lloyd J. Old Memorial Award and is supported by an Irvington Institute postdoctoral fellowship from the Cancer Research Institute., Vougny, Marie-Christine, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Curie
Subjects: MESH: Minor Histocompatibility Antigens, MESH: Nuclear Receptor Subfamily 1, Group F, Member 3, Receptors, Antigen, T-Cell, alpha-beta, MESH: Chemotaxis, Leukocyte, MESH: Urinary Tract Infections, Lymphocyte Activation, MESH: Mice, Knockout, MESH: Histocompatibility Antigens Class I, MESH: Promyelocytic Leukemia Zinc Finger Protein, Mice, 0302 clinical medicine, Promyelocytic Leukemia Zinc Finger Protein, MESH: Animals, Mice, Knockout, 0303 health sciences, education.field_of_study, Lymphokines, MESH: Receptors, Antigen, T-Cell, alpha-beta, Microbiota, MESH: Polymorphism, Single Nucleotide, General Medicine, Nuclear Receptor Subfamily 1, Group F, Member 3, Natural killer T cell, MESH: Crosses, Genetic, Chemotaxis, Leukocyte, medicine.anatomical_structure, Phenotype, Radiation Chimera, Urinary Tract Infections, MESH: Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor, MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Kruppel-Like Transcription Factors, Research Article, MESH: Lymphocyte Count, [SDV.IMM] Life Sciences [q-bio]/Immunology, Lymphoid Tissue, MESH: Radiation Chimera, MESH: Mice, Transgenic, T cell, Population, Congenic, Kruppel-Like Transcription Factors, Mice, Transgenic, Mucosal associated invariant T cell, Biology, MESH: Phenotype, Polymorphism, Single Nucleotide, Minor Histocompatibility Antigens, 03 medical and health sciences, Mice, Congenic, MESH: Mice, Congenic, MESH: Mice, Inbred C57BL, MESH: Germ-Free Life, medicine, Animals, Germ-Free Life, Humans, MESH: Microbiota, Lymphocyte Count, Receptors, Cytokine, education, MESH: Lymphocyte Activation, MESH: Mice, Crosses, Genetic, 030304 developmental biology, MESH: Humans, MESH: Lymphokines, T-cell receptor, Histocompatibility Antigens Class I, Laboratory mouse, Gene rearrangement, Molecular biology, MESH: Receptors, Cytokine, Mice, Inbred C57BL, Disease Models, Animal, MESH: Natural Killer T-Cells, MESH: Lymphoid Tissue, Natural Killer T-Cells, MESH: Disease Models, Animal, Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor, Immunologic Memory, MESH: Female, 030215 immunology
Abstract: Mucosal-associated invariant T cells (MAITs) have potent antimicrobial activity and are abundant in humans (5%-10% in blood). Despite strong evolutionary conservation of the invariant TCR-alpha chain and restricting molecule MR1, this population is rare in laboratory mouse strains (approximate to 0.1% in lymphoid organs), and lack of an appropriate mouse model has hampered the study of MAIT biology. Herein, we show that MAITs are 20 times more frequent in clean wild-derived inbred CAST/EiJ mice than in C57BL/6J mice. Increased MAIT frequency was linked to one CAST genetic trait that mapped to the TCR-alpha locus and led to higher usage of the distal V alpha segments, including V alpha 19. We generated a MAIT(hl) congenic strain that was then crossed to a transgenic Rorcgt-GFP reporter strain. Using this tool, we characterized polyclonal mouse MAITs as memory (CD44(+)) CD4(-)CD8(lo/neg) T cells with tissue-homing properties (CCR6*CCR7(-)). Similar to human MAITs, mouse MAITs expressed the cytokine receptors IL-7R, IL-18R alpha, and IL-12R beta and the transcription factors promyelocytic leukemia zinc finger (PLZF) and RAR-related orphan receptory gamma (R0R gamma t). Mouse MAITs produced Th1/2/17 cytokines upon TCR stimulation and recognized a bacterial compound in an MR1-dependent manner. During experimental urinary tract infection, MAITs migrated to the bladder and decreased bacterial load. Our study demonstrates that the MAIT(hi) congenic strain allows phenotypic and functional characterization of naturally occurring mouse MAITs in health and disease.
Published: 2015

3. Epigenetic control of Tcrb gene rearrangement

Author: Aleksandra Pekowska, Pierre Ferrier, Salvatore Spicuglia, Joaquin Zacarias-Cabeza, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)
Subjects: Epigenomics, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, Immunology, MESH: Epigenomics, Locus (genetics), Biology, 03 medical and health sciences, 0302 clinical medicine, Recombinase, Animals, Humans, Immunology and Allergy, Recombination signal sequences, MESH: Animals, Gene, Alleles, 030304 developmental biology, Recombination, Genetic, Genetics, 0303 health sciences, MESH: Humans, MESH: Receptors, Antigen, T-Cell, alpha-beta, MESH: Alleles, V(D)J recombination, T-cell receptor, Gene rearrangement, Allelic exclusion, MESH: T-Lymphocytes, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Recombination, Genetic, 030215 immunology
Abstract: International audience; V(D)J recombination assembles antigen receptor genes from germline V, D and J segments during lymphocyte development. In αβT-cells, this leads to the subsequent expression of T-cell receptor (TCR) β and α chains. Generally, V(D)J recombination is closely controlled at various levels, including cell-type and cell-stage specificities, order of locus/gene segment recombination, and allele usage to mediate allelic exclusion. Many of these controls rely on the modulation of gene accessibility to the recombination machinery, involving not only biochemical changes in chromatin arrangement and structural modifications of chromosomal organization and positioning, but also the refined composition of the recombinase targets, the so-called recombination signal sequences. Here, we summarize current knowledge regarding the regulation of V(D)J recombination at the Tcrb gene locus, certainly one for which these various levels of control and regulatory components have been most extensively investigated.
Published: 2010

4. Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying the TCRβ-HOXA rearrangement: a study of the Groupe Francophone de Cytogénétique Hématologique

Author: C. Charrin, Anne Hagemeijer, Carole Barin, M J Mozzicconacci, Barbara Cauwelier, Christine Lefebvre, Bruno Verhasselt, Isabelle Luquet, M.J. Gregoire, Philippe Jonveaux, Hélène Cavé, Barbara De Moerloose, Christine Terré, Kim De Keersmaecker, Anne De Paepe, G Plessis, F Sigaux, Nicole Dastugue, Bruce Poppe, Michel Lessard, B Laurence, Laurent Mauvieux, Hélène Antoine-Poirel, Marina Lafage-Pochitaloff, Francine Mugneret, Emmanuelle Clappier, J van den Akker, J Soulier, C Graux, Yves Benoit, Jan Cools, Carine Gervais, Franki Speleman, Pascale Cornillet-Lefebvre, Marie-Pierre Pages, C Chalas, Dominique Leroux, N. Van Roy, Christine Perot, Pierre Heimann, Roland Berger, Center for Medical Genetics [Ghent], Ghent University Hospital, Laboratoire de Biochimie Génétique, Hôpital Robert Debré, Laboratoire d'Hématologie, CHU Strasbourg, CHU Bretonneau, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire Central d'Anatomie et de Cytologie Pathologiques [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Génétique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier de Versailles André Mignot (CHV), Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Service de Génétique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Bases moléculaires de la progression tumorale -Groupe de Recherche sur les Lymphomes, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR73, Centre for Medical genetics, Hôpital UCL-St Luc, Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Medical Genetics, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Centre for Molecular Diagnostics, Department of Pediatric Hematology/Oncology, Department of Human Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre for Human Genetics, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre for Medical Genetics, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Université Pierre et Marie Curie - Paris 6 (UPMC) - Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Dijon (CHU Dijon), Laboratoire de Cytopathologie, Hôpital Edouard Herriot, Laboratoire de Génétique, CHU Nancy, Institut Paoli Calmettes, CHU Versailles, Centre Hospitalier de Versailles (CHV), CHU Reims, Hôpital Robert Debré - CHU Reims, Service de génétique, CHU Caen - Hôpital Clémenceau, Université Joseph Fourier - Grenoble 1 (UJF) - Institut National de la Santé et de la Recherche Médicale (INSERM) - IFR73, Université Paris Diderot - Paris 7 (UP7) - Institut National de la Santé et de la Recherche Médicale (INSERM), University Hospital Erasme, Hôpital Necker - Enfants malades, Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris Descartes - Paris 5 (UPD5), Hôpital Purpan, and Duley, Samuel
Subjects: Male, Cancer Research, Receptors, Antigen, T-Cell, alpha-beta, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH: Receptor, Notch1, Translocation, Genetic, 0302 clinical medicine, Immunophenotyping, MESH: Child, Leukemia-Lymphoma, Adult T-Cell, MESH: Leukemia-Lymphoma, Adult T-Cell, Receptor, Notch1, Child, Chromosomal inversion, 0303 health sciences, MESH: Middle Aged, MESH: Receptors, Antigen, T-Cell, alpha-beta, hemic and immune systems, Hematology, Middle Aged, MESH: Gene Rearrangement, T-Lymphocyte, MESH: Translocation, Genetic, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Female, Chromosome Deletion, Adult, Transcriptional Activation, medicine.medical_specialty, Adolescent, MESH: Immunophenotyping, MESH: Chromosome Deletion, chemical and pharmacologic phenomena, Chromosomal rearrangement, Biology, Gene Rearrangement, T-Lymphocyte, 03 medical and health sciences, Acute lymphocytic leukemia, MESH: Homeodomain Proteins, medicine, Humans, 030304 developmental biology, Homeodomain Proteins, MESH: Adolescent, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, T-cell receptor, Cytogenetics, MESH: Adult, Gene rearrangement, medicine.disease, Molecular biology, MESH: Male, Homeobox A10 Proteins, Chromosome Inversion, MESH: Inversion, Chromosome, MESH: Transcriptional Activation, MESH: Female, Comparative genomic hybridization
Abstract: International audience; Recently, we and others described a new chromosomal rearrangement, that is, inv(7)(p15q34) and t(7;7)(p15;q34) involving the T-cell receptor beta (TCRbeta) (7q34) and the HOXA gene locus (7p15) in 5% of T-cell acute lymphoblastic leukemia (T-ALL) patients leading to transcriptional activation of especially HOXA10. To further address the clinical, immunophenotypical and molecular genetic findings of this chromosomal aberration, we studied 330 additional T-ALLs. This revealed TCRbeta-HOXA rearrangements in five additional patients, which brings the total to 14 cases in 424 patients (3.3%). Real-time quantitative PCR analysis for HOXA10 gene expression was performed in 170 T-ALL patients and detected HOXA10 overexpression in 25.2% of cases including all the cases with a TCRbeta-HOXA rearrangement (8.2%). In contrast, expression of the short HOXA10 transcript, HOXA10b, was almost exclusively found in the TCRbeta-HOXA rearranged cases, suggesting a specific role for the HOXA10b short transcript in TCRbeta-HOXA-mediated oncogenesis. Other molecular and/or cytogenetic aberrations frequently found in subtypes of T-ALL (SIL-TAL1, CALM-AF10, HOX11, HOX11L2) were not detected in the TCRbeta-HOXA rearranged cases except for deletion 9p21 and NOTCH1 activating mutations, which were present in 64 and 67%, respectively. In conclusion, this study defines TCRbeta-HOXA rearranged T-ALLs as a distinct cytogenetic subgroup by clinical, immunophenotypical and molecular genetic characteristics.
Published: 2006

5. T cell repertoire and Epstein–Barr virus-specific T cell response in chronic active Epstein–Barr virus infection: A case study

Author: Christophe Ferrand, Régine Vivien, Anne Moreau, Béatrice Clémenceau, Henri Vié, Sébastien Barbarot, Joëlle Gaschet, Mohamed Hamidou, Pierre Tiberghien, Géraldine Gallot, M. Coste-Burel, Saas, Philippe, Recherches en cancérologie, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: Cytotoxicity, Immunologic, Male, Epstein-Barr Virus Infections, Herpesvirus 4, Human, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, Epitopes, T-Lymphocyte, Genes, MHC Class I, Cell Separation, MESH: T-Lymphocyte Subsets, CD8-Positive T-Lymphocytes, medicine.disease_cause, MESH: Lymphoproliferative Disorders, 0302 clinical medicine, T-Lymphocyte Subsets, hemic and lymphatic diseases, Chlorocebus aethiops, Immunology and Allergy, Cytotoxic T cell, MESH: Animals, MESH: Peptide Fragments, Skin, 0303 health sciences, MESH: Receptors, Antigen, T-Cell, alpha-beta, MESH: Epstein-Barr Virus Infections, MESH: Vasculitis, MESH: Genes, MHC Class I, Natural killer T cell, MESH: CD8-Positive T-Lymphocytes, 3. Good health, MESH: COS Cells, MESH: Leukocytes, Mononuclear, medicine.anatomical_structure, 030220 oncology & carcinogenesis, COS Cells, MESH: Complementarity Determining Regions, [SDV.IMM]Life Sciences [q-bio]/Immunology, Adult, Vasculitis, [SDV.IMM] Life Sciences [q-bio]/Immunology, T cell, Immunology, Biology, Transfection, MESH: Cell Separation, Peripheral blood mononuclear cell, Cell Line, MESH: Epitopes, T-Lymphocyte, MESH: Coculture Techniques, TCIRG1, Viral Proteins, 03 medical and health sciences, MESH: Skin, medicine, Animals, Humans, MESH: Cytotoxicity, Immunologic, Antigen-presenting cell, 030304 developmental biology, MESH: Humans, Tumor Necrosis Factor-alpha, MESH: Transfection, MESH: Chronic Disease, MESH: Adult, MESH: Herpesvirus 4, Human, Complementarity Determining Regions, MESH: Viral Proteins, MESH: Cercopithecus aethiops, Epstein–Barr virus, Virology, Coculture Techniques, Lymphoproliferative Disorders, Peptide Fragments, MESH: Male, MESH: DNA, Viral, MESH: Cell Line, MESH: T-Lymphocytes, MESH: Tumor Necrosis Factor-alpha, Chronic Disease, DNA, Viral, Leukocytes, Mononuclear, MESH: T-Lymphocytes, Cytotoxic, Memory T cell, T-Lymphocytes, Cytotoxic
Abstract: International audience; In a patient with chronic active Epstein-Barr virus infection associated with vasculitis and fulminant CD4+ T cell lymphoproliferative disorder, we probed the peripheral blood mononuclear cells (PBMC) for the presence of an EBV-specific T cell repertoire and tested the possible relationship between the lymphocytic infiltrate and the EBV-specific T cell response. Our results give credence to the presence of an apparently normal EBV-specific memory T cell response after in vitro reactivation of the patient's PBMC with autologous infected B lymphoblastoid cell lines. In keeping with the characterization of the vasculitis, certain T cell subsets were detected after expansion of skin lesion-infiltrating lymphocytes and were found to be infected with EBV. These particular T cell expansions were neither the effectors nor the targets of the in vitro reactivated EBV-specific T cells, thus excluding a simple relationship between EBV, the skin lesions, and the T cell expansions frequently observed in these patients.
Published: 2006

6. Extrathymic T Cell Lymphopoiesis

Author: Pierre Vassalli, Philippe Kourilsky, Sylvie Darche, Delphine Guy-Grand, Orly Azogui, Michel C. Nussenzweig, Susanna Celli, Biologie Moléculaire du Gène, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Molecular Immunology and the Howard Hughes Institute, Rockefeller University [New York], and Université de Genève = University of Geneva (UNIGE)
Subjects: Cellular differentiation, Genes, RAG-1, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, extrathymic differentiation, MESH: Lymph Nodes, MESH: T-Lymphocyte Subsets, MESH: Mice, Knockout, Mice, Peyer's Patches, recombinase activating gene, T-Lymphocyte Subsets, Immunology and Allergy, MESH: Animals, Lymph node, Mice, Knockout, MESH: Receptors, Antigen, T-Cell, alpha-beta, gut intraepithelial lymphocytes, Lymphopoiesis, hemic and immune systems, Cell Differentiation, Receptors, Antigen, T-Cell, gamma-delta, MESH: Genes, RAG-1, MESH: Lymphopoiesis, Gut Epithelium, medicine.anatomical_structure, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Luminescent Proteins, MESH: Cell Differentiation, MESH: Mice, Transgenic, T cell, Immunology, Green Fluorescent Proteins, Double negative, T lymphocytes, Mice, Nude, Mice, Transgenic, Biology, Article, Lymphocyte Depletion, MESH: Receptors, Interleukin-2, MESH: Green Fluorescent Proteins, MESH: Receptors, Antigen, T-Cell, gamma-delta, RAG2, MESH: Mice, Nude, medicine, Animals, MESH: Mice, MESH: Lymphocyte Depletion, Receptors, Interleukin-2, Luminescent Proteins, MESH: T-Lymphocytes, MESH: Peyer's Patches, Intraepithelial lymphocyte, mucosal immunity, Lymph Nodes
Abstract: In the absence of thymopoiesis, T lymphocytes are nevertheless present, mainly in the gut epithelium. Ontogeny of the extrathymic pathway and the extent of its involvement in euthymic mice are controversial. These questions have been addressed by assessing the expression of recombinase activating gene (RAG) through the use of green fluorescent protein RAG2 transgenic mouse models. In athymic mice, T lymphopoiesis occurs mainly in the mesenteric lymph node and less in the Peyer's patches. Ontogenic steps of this lymphopoiesis resemble those of thymopoiesis, but with an apparent bias toward gamma delta T cell production and with a paucity of oligoclonal alpha beta T cells possibly resulting from a deficit in positive selection. Whether in athymic or euthymic mice, neither T intraepithelial lymphocytes (IEL) nor cryptopatch cells (reported to contain precursors of IEL) displayed fluorescence indicating recent RAG protein synthesis. Newly made T cells migrate from the mesenteric node into the thoracic duct lymph to reach the gut mucosa. In euthymic mice, this extrathymic pathway is totally repressed, except in conditions of severe lymphocytic depletion. Thus, in normal animals, all gut T IEL, including CD8 alpha alpha(+) cells, are of thymic origin, CD8 alpha alpha(+) TCR alpha beta(+) IEL being the likely progeny of double negative NK1-1(-) thymocytes, which show polyclonal V alpha and V beta repertoires.
Published: 2003

7. The RAG2 C-terminus and ATM protect genome integrity by controlling antigen receptor gene cleavage

Author: Panagiotis Ntziachristos, Ludovic Deriano, David Roth, Iannis Aifantis, Mariann Micsinai, Jane A. Skok, Yuval Kluger, Julie Chaumeil, New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Yale School of Medicine [New Haven, Connecticut] (YSM), University of Pennsylvania, Développement lymphocytaire et Oncogénèse, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), This work is supported by the National Institute of Health: RO1GM086852 and R56NIAIDAI099111 (J.A.S.), CA-16359 (Y.K.), RO1CA133379, RO1CA105129, RO1CA149655, RO1CA173636 and RO1GM088847 (I.A.), and CA104588 (D.B.R.). J.A.S is an LLS scholar. J.C. is an Irvington Institute Fellow of the Cancer Research Institute. M.M. was supported by an NSF IGERT 0333389. P.N. is supported by the Lady Tata Memorial Trust for Leukemia. I.A. is also supported by the Leukemia and Lymphoma Society (TRP grant), the Chemotherapy Foundation, the V Foundation of Cancer Research and the William Lawrence Blanche Hughes Foundation, and is an early Career Scientist of the Howard Hughes Medical Institute. L.D. is supported by the Institut Pasteur, the CNRS, the Fondation pour la Recherche Medicale, the Ville de Paris, and by the European Research Council (ERC starting grant agreement no. 310917)., European Project: 310917,EC:FP7:ERC,ERC-2012-StG_20111109,LYMPHOONCOGENOMICS(2013), Yale University School of Medicine, University of Pennsylvania [Philadelphia], and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: Genome instability, delta-Chain T-Cell Antigen Receptor, Receptors, Antigen, T-Cell, alpha-beta, General Physics and Astronomy, Chromosomal translocation, Ataxia Telangiectasia Mutated Proteins, Mice, 0302 clinical medicine, Receptors, Medicine and Health Sciences, MESH: Animals, Ataxia Telangiectasia Mutated Proteins/*metabolism, MESH: Ataxia Telangiectasia Mutated Proteins, Genetics, 0303 health sciences, Multidisciplinary, MESH: Receptors, Antigen, T-Cell, alpha-beta, MESH: Genomic Instability, MESH: Gene Rearrangement, delta-Chain T-Cell Antigen Receptor, DNA-Binding Proteins, medicine.anatomical_structure, Antigen, MESH: Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor, [SDV.IMM]Life Sciences [q-bio]/Immunology, alpha-beta/genetics, DNA-Binding Proteins/*chemistry/*metabolism, Gene Rearrangement, T cell, Gene Rearrangement, delta-Chain T-Cell Antigen Receptor, Biology, Cleavage (embryo), DNA-binding protein, MESH: Genetic Loci, General Biochemistry, Genetics and Molecular Biology, Article, Genomic Instability, 03 medical and health sciences, RAG2, medicine, Animals, MESH: Mice, 030304 developmental biology, Biology and Life Sciences, General Chemistry, Gene rearrangement, T-Cell, Genetic Loci, alpha-Chain T-Cell Antigen Receptor, Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor, MESH: DNA-Binding Proteins, 030215 immunology
Abstract: International audience; Tight control of antigen-receptor gene rearrangement is required to preserve genome integrity and prevent the occurrence of leukaemia and lymphoma. Nonetheless, mistakes can happen, leading to the generation of aberrant rearrangements, such as Tcra/d-Igh inter-locus translocations that are a hallmark of ataxia telangiectasia-mutated (ATM) deficiency. Current evidence indicates that these translocations arise from the persistence of unrepaired breaks converging at different stages of thymocyte differentiation. Here we show that a defect in feedback control of RAG2 activity gives rise to bi-locus breaks and damage on Tcra/d and Igh in the same T cell at the same developmental stage, which provides a direct mechanism for generating these inter-locus rearrangements. Both the RAG2 C-terminus and ATM prevent bi-locus RAG-mediated cleavage through modulation of three-dimensional conformation (higher-order loops) and nuclear organization of the two loci. This limits the number of potential substrates for translocation and provides an important mechanism for protecting genome stability.
Published: 2013

8. GATA-3 promotes T-cell specification by repressing B-cell potential in pro–T cells in mice

Author: Ana Cumano, Odile Richard-Le Goff, Roel G. J. Klein Wolterink, Rudolf W. Hendriks, Fabrice Lemaître, Milena Hasan, James P. Di Santo, Marcos E. García-Ojeda, Immunité Innée, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Développement des Lymphocytes, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Cellule Pasteur, Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Dynamiques des Réponses Immunes, Centre d'Immunologie Humaine (CIH), This work was supported by a fellowship from the Pasteur Foundation (M.E.G.-O.), by grants from the Huygens Scholarship Program and the Royal Netherlands Academy for Arts and Sciences (both the Netherlands) and by the Ligue Nationale Contre le Cancer (France, R.G.J.K.W.). This work was also supported by grants from the Institut Pasteur, the Inserm, and the Ligue Nationale Contre le Cancer (all in France, J.P.D.)., Pulmonary Medicine, Immunology, and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, MESH: Signal Transduction, Receptors, Antigen, T-Cell, alpha-beta, MESH: Flow Cytometry, MESH: Receptor, Notch1, Biochemistry, MESH: Mice, Knockout, Mice, 0302 clinical medicine, Inside Blood, b-lymphocytes, MESH: Animals, Receptor, Notch1, Cells, Cultured, Mice, Knockout, 0303 health sciences, MESH: Receptors, Antigen, T-Cell, alpha-beta, Cell Differentiation, Hematology, MESH: Transcription Factors, Flow Cytometry, Cell biology, medicine.anatomical_structure, embryonic structures, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, biological phenomena, cell phenomena, and immunity, medicine.symptom, Signal Transduction, MESH: Cells, Cultured, MESH: Cell Differentiation, T cell, Immunology, gata3 gene, GATA3 Transcription Factor, Thymus Gland, Biology, 03 medical and health sciences, MESH: B-Lymphocytes, MESH: GATA3 Transcription Factor, medicine, Animals, Notch1 signaling, Cell Lineage, Transcription factor, t-lymphocytes, MESH: Mice, B cell, 030304 developmental biology, Cell Biology, MESH: Thymus Gland, MESH: Cell Lineage, MESH: Male, MESH: T-Lymphocytes, Mechanism of action, MESH: Female, 030215 immunology, Transcription Factors
Abstract: International audience; Transcription factors orchestrate T-lineage differentiation in the thymus. One critical checkpoint involves Notch1 signaling that instructs T-cell commitment at the expense of the B-lineage program. While GATA-3 is required for T-cell specification, its mechanism of action is poorly understood. We show that GATA-3 works in concert with Notch1 to commit thymic progenitors to the T-cell lineage via 2 distinct pathways. First, GATA-3 orchestrates a transcriptional “repertoire” that is required for thymocyte maturation up to and beyond the pro–T-cell stage. Second, GATA-3 critically suppresses a latent B-cell potential in pro–T cells. As such, GATA-3 is essential to sealing in Notch-induced T-cell fate in early thymocyte precursors by promoting T-cell identity through the repression of alternative developmental options.
Published: 2013

9. Anti-tumour immunotherapy with Vγ9Vδ2 T lymphocytes: from the bench to the bedside

Author: Mounia Sabrina Braza, Bernard Klein, Cellules souches normales et cancéreuses, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Institut de recherche en biothérapie (IRB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Frei, Monique
Subjects: Receptors, Antigen, T-Cell, alpha-beta, medicine.medical_treatment, Lymphocyte, MESH: Antigens, Neoplasm, MESH: Translational Medical Research, MESH: Adjuvants, Immunologic, MESH: T-Lymphocyte Subsets, Adaptive Immunity, CD8-Positive T-Lymphocytes, Immunotherapy, Adoptive, T-Lymphocytes, Regulatory, Translational Research, Biomedical, 0302 clinical medicine, Cancer immunotherapy, T-Lymphocyte Subsets, Neoplasms, MESH: Neoplasms, Immunologic Surveillance, Cells, Cultured, Clinical Trials as Topic, 0303 health sciences, MESH: Receptors, Antigen, T-Cell, alpha-beta, Diphosphonates, MESH: Dendritic Cells, Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor, Receptors, Antigen, T-Cell, gamma-delta, Hematology, Acquired immune system, MESH: Gene Rearrangement, delta-Chain T-Cell Antigen Receptor, MESH: CD8-Positive T-Lymphocytes, 3. Good health, Killer Cells, Natural, medicine.anatomical_structure, MESH: Immunotherapy, Adoptive, MESH: Tumor Escape, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Immunity, Innate, immunotherapy, monoclonal antibodies, MESH: Cells, Cultured, MESH: Killer Cells, Natural, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Clinical Trials as Topic, MESH: Diphosphonates, T cell, Gene Rearrangement, delta-Chain T-Cell Antigen Receptor, haematological oncology, 03 medical and health sciences, Adjuvants, Immunologic, Antigen, Antigens, Neoplasm, gamma delta T lymphocytes, MESH: Receptors, Antigen, T-Cell, gamma-delta, medicine, Humans, cancer, 030304 developmental biology, MESH: Immunologic Surveillance, MESH: Humans, business.industry, MESH: T-Lymphocytes, Regulatory, Mesenchymal Stem Cells, Dendritic Cells, Immunotherapy, Gene rearrangement, T lymphocyte, Immunity, Innate, MESH: Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor, Immunology, MESH: Mesenchymal Stromal Cells, Tumor Escape, business, MESH: T-Lymphocytes, Cytotoxic, MESH: Adaptive Immunity, T-Lymphocytes, Cytotoxic, 030215 immunology
Abstract: International audience; Gamma delta (γδ) Τ cells are non-conventional T lymphocyte effectors that can interact with and eradicate tumour cells. Several data demonstrate that these T cells, which are implicated in the first line of defence against pathogens, have anti-tumour activity against many cancers and suggest that γδ Τ cell-mediated immunotherapy is feasible and might induce objective tumour responses. Due to the importance of γδ Τ lymphocytes in the induction and control of immunity, a complete understanding of their biology is crucial for the development of a potent cancer immunotherapy. This review discusses recent advances in γδ Τ basic research and data from clinical trials on the use of γδ Τ cells in the treatment of different cancers. It analyses how this knowledge might be applied to develop new strategies for the clinical manipulation and the potentiation of γδ Τ lymphocyte activity in cancer immunotherapy.
Published: 2013

10. Molecular features of hepatosplenic T-cell lymphoma unravels potential novel therapeutic targets.: Molecular Signature of Hepatosplenic T-cell Lymphoma

Author: Travert, Marion, Huang, Yenlin, De Leval, Laurence, Martin-Garcia, Nadine, Delfau-Larue, Marie-Helene, Berger, Françoise, Bosq, Jacques, Brière, Josette, Soulier, Jean, Macintyre, Elizabeth, Marafioti, Teresa, De Reyniès, Aurélien, Gaulard, Philippe, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Department of Anatomic Pathology, Chang Gung Memorial Hospital [Taipei] (CGMH), Service de Pathologie Clinique, Université de Lausanne (UNIL)-Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV)-Institut Universitaire de Pathologie, Service d'immunologie biologique, Centre de Biologie et de Pathologie, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital Renée Sabran [CHU - HCL], Hospices Civils de Lyon (HCL), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR), Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anatomo-pathologie [Paris], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie, dermatologie, oncologie, Oncodermatologie, immunologie et cellules souches cutanées (IDO (U976 / UMR_S 976)), Service hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Department of histopathology, University College Hospital, (le programme) Cartes d'identité des tumeurs (CIT), Ligue Nationales Contre le Cancer (LNCC), This work is part of the Carte d'Identité des Tumeurs (CIT) program (http://cit.liguecancer.net/index.php/en) from the Ligue Nationale Contre le Cancer and of the Tenomic project inserm-00730464, version 1 - 10 Sep 2012 supported by a Programme Hospitalier de Recherche Clinique and the Institut National du Cancer (INCa). This work was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM), the Institut National du Cancer (INCa), the Plan cancer of the Belgian government, and the Association pour la Recherche Thérapeutique, Génétique et Immunologique dans les Lymphomes (ARTGIL). M.T. was supported by the Fondation pour la Recherche Médicale (DEQ 2010/0318253), Université de Lausanne = University of Lausanne (UNIL)-Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV)-Institut Universitaire de Pathologie, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
Subjects: MESH: Base Sequence, MESH: Protein-Tyrosine Kinases, MESH: Gene Expression Profiling, MESH: Isochromosomes, MESH: Liver Neoplasms, MESH: Receptors, Antigen, T-Cell, gamma-delta, MESH: Intracellular Signaling Peptides and Proteins, MESH: Molecular Targeted Therapy, MESH: Chromosome Aberrations, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Genes, Neoplasm, MESH: Aged, MESH: Humans, MESH: Middle Aged, MESH: Molecular Sequence Data, MESH: Receptors, Antigen, T-Cell, alpha-beta, MESH: Adult, MESH: Gene Expression Regulation, Neoplastic, MESH: Cell Lineage, MESH: Splenic Neoplasms, MESH: Cluster Analysis, MESH: Male, MESH: Drug Resistance, Neoplasm, MESH: Crystallins, MESH: Young Adult, MESH: Tumor Markers, Biological, MESH: Lymphoma, T-Cell, MESH: Membrane Proteins, MESH: Female
Abstract: International audience; The pathogenesis of hepatosplenic T-cell lymphoma (HSTL), a rare entity mostly derived from γδ T cells and usually with a fatal outcome, remains largely unknown. In this study, HSTL samples (7γδ and 2αβ) and the DERL2 HSTL cell line were subjected to combined gene-expression profiling and array-based comparative genomic hybridization. Compared with other T-cell lymphomas, HSTL had a distinct molecular signature irrespective of TCR cell lineage. Compared with peripheral T-cell lymphoma, not otherwise specified and normal γδ T cells, HSTL overexpressed genes encoding NK-cell-associated molecules, oncogenes (FOS and VAV3), the sphingosine-1-phosphatase receptor 5 involved in cell trafficking, and the tyrosine kinase SYK, whereas the tumor-suppressor gene AIM1 (absent in melanoma 1) was among the most down-expressed. We found highly methylated CpG islands of AIM1 in DERL2 cells, and decitabine treatment induced a significant increase in AIM1 transcripts. Syk was present in HSTL cells and DERL2 cells contained phosphorylated Syk and were sensitive to a Syk inhibitor in vitro. Genomic profiles confirmed recurrent isochromosome 7q (n = 6/9) without alterations at the SYK and AIM1 loci. Our results identify a distinct molecular signature for HSTL and highlight oncogenic pathways that offer rationale for exploring new therapeutic options such as Syk inhibitors and demethylating agents.
Published: 2012

11. Molecular features of hepatosplenic T-cell lymphoma unravels potential novel therapeutic targets.: Molecular Signature of Hepatosplenic T-cell Lymphoma

Author: Travert, Marion, Huang, Yenlin, de Leval, Laurence, Martin-Garcia, Nadine, Delfau-Larue, Marie-Helene, Berger, Françoise, Bosq, Jacques, Brière, Josette, Soulier, Jean, Macintyre, Elizabeth, Marafioti, Teresa, de Reyniès, Aurélien, Gaulard, Philippe, Guellaen, Georges, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Department of Anatomic Pathology, Chang Gung Memorial Hospital [Taipei] (CGMH), Service de Pathologie Clinique, Université de Lausanne = University of Lausanne (UNIL)-Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV)-Institut Universitaire de Pathologie, Service d'immunologie biologique, Centre de Biologie et de Pathologie, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital Renée Sabran [CHU - HCL], Hospices Civils de Lyon (HCL), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR), Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie, dermatologie, oncologie, Oncodermatologie, immunologie et cellules souches cutanées (IDO (U976 / UMR_S 976)), Service hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Department of histopathology, University College Hospital, (le programme) Cartes d'identité des tumeurs (CIT), Ligue Nationales Contre le Cancer (LNCC), and This work is part of the Carte d'Identité des Tumeurs (CIT) program (http://cit.liguecancer.net/index.php/en) from the Ligue Nationale Contre le Cancer and of the Tenomic project inserm-00730464, version 1 - 10 Sep 2012 supported by a Programme Hospitalier de Recherche Clinique and the Institut National du Cancer (INCa). This work was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM), the Institut National du Cancer (INCa), the Plan cancer of the Belgian government, and the Association pour la Recherche Thérapeutique, Génétique et Immunologique dans les Lymphomes (ARTGIL). M.T. was supported by the Fondation pour la Recherche Médicale (DEQ 2010/0318253)
Subjects: MESH: Base Sequence, MESH: Protein-Tyrosine Kinases, MESH: Gene Expression Profiling, MESH: Isochromosomes, MESH: Liver Neoplasms, MESH: Receptors, Antigen, T-Cell, gamma-delta, MESH: Intracellular Signaling Peptides and Proteins, MESH: Molecular Targeted Therapy, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Chromosome Aberrations, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Genes, Neoplasm, MESH: Aged, MESH: Humans, MESH: Middle Aged, MESH: Molecular Sequence Data, MESH: Receptors, Antigen, T-Cell, alpha-beta, MESH: Adult, MESH: Gene Expression Regulation, Neoplastic, MESH: Cell Lineage, MESH: Splenic Neoplasms, MESH: Cluster Analysis, MESH: Male, MESH: Drug Resistance, Neoplasm, MESH: Crystallins, MESH: Young Adult, MESH: Tumor Markers, Biological, MESH: Lymphoma, T-Cell, MESH: Membrane Proteins, MESH: Female
Abstract: International audience; The pathogenesis of hepatosplenic T-cell lymphoma (HSTL), a rare entity mostly derived from γδ T cells and usually with a fatal outcome, remains largely unknown. In this study, HSTL samples (7γδ and 2αβ) and the DERL2 HSTL cell line were subjected to combined gene-expression profiling and array-based comparative genomic hybridization. Compared with other T-cell lymphomas, HSTL had a distinct molecular signature irrespective of TCR cell lineage. Compared with peripheral T-cell lymphoma, not otherwise specified and normal γδ T cells, HSTL overexpressed genes encoding NK-cell-associated molecules, oncogenes (FOS and VAV3), the sphingosine-1-phosphatase receptor 5 involved in cell trafficking, and the tyrosine kinase SYK, whereas the tumor-suppressor gene AIM1 (absent in melanoma 1) was among the most down-expressed. We found highly methylated CpG islands of AIM1 in DERL2 cells, and decitabine treatment induced a significant increase in AIM1 transcripts. Syk was present in HSTL cells and DERL2 cells contained phosphorylated Syk and were sensitive to a Syk inhibitor in vitro. Genomic profiles confirmed recurrent isochromosome 7q (n = 6/9) without alterations at the SYK and AIM1 loci. Our results identify a distinct molecular signature for HSTL and highlight oncogenic pathways that offer rationale for exploring new therapeutic options such as Syk inhibitors and demethylating agents.
Published: 2012

12. Invariant natural killer T-cell-deficient mice display increased CCl₄ -induced hepatitis associated with CXCL1 over-expression and neutrophil infiltration

Author: Lisbonne, Mariette, L'Helgoualc'H, Annie, Nauwelaers, Gwendoline, Turlin, Bruno, Lucas, Catherine, Herbelin, André, Piquet-Pellorce, Claire, Samson, Michel, Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), departement de pathologie, Laboratoire de biochimie générale, Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140, Signalisation et Réponses aux Agents Infectieux et Chimiques ( SeRAIC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ), Cytokines, hématopoïèse et réponse immune ( CHRI ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Rennes (UR), and CHU Pontchaillou [Rennes]
Subjects: CXCL1/KC, Neutrophils, Chemokine CXCL1, Receptors, Antigen, T-Cell, alpha-beta, MESH : Carbon Tetrachloride, Apoptosis, MESH : Hepatocytes, Hepatitis, Animal, MESH: Neutrophils, MESH: Mice, Knockout, Hepatitis, MESH : Neutrophils, MESH: Hepatocytes, Mice, Cell Movement, MESH : Cell Movement, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, MESH : Matrix Metalloproteinase 8, Carbon Tetrachloride, MESH: Cell Movement, Cells, Cultured, Mice, Knockout, Alanine, MESH: Receptors, Antigen, T-Cell, alpha-beta, MESH : Acute Disease, Neutrophil, MESH: Hepatitis, Animal, MESH : Chemokine CXCL1, Matrix Metalloproteinase 8, MESH : Receptors, Antigen, T-Cell, alpha-beta, Liver, Acute Disease, MESH: Acute Disease, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Cells, Cultured, MESH: Alanine, MESH : Aspartate Aminotransferases, MESH: Aspartate Aminotransferases, MESH : Mice, MESH : Cells, Cultured, Animals, MESH: Chemokine CXCL1, Aspartate Aminotransferases, MESH: Mice, MESH: Apoptosis, MESH: Carbon Tetrachloride, MESH : Liver, MESH : Natural Killer T-Cells, MESH: Natural Killer T-Cells, MESH: Matrix Metalloproteinase 8, Hepatocytes, Invariant NKT cells, MESH : Mice, Knockout, Natural Killer T-Cells, MESH : Animals, MESH : Alanine, MESH : Hepatitis, Animal, MESH : Apoptosis, MESH: Liver
Abstract: International audience; Invariant natural killer T (iNKT) cells are involved in the intrahepatic immune response and in hepatitis. In particular, iNKT lymphocytes are responsible for hepatocyte death in concanavalin A-induced hepatitis in mice. We examined the role of iNKT cells in acute hepatitis induced by a hepatotoxic agent, carbon tetrachloride (CCl(4) ). WT and iNKT cell-deficient (Jα18(-/-) ) mice were challenged with a single dose of 2.4 g/kg CCl(4) and both hepatic physiopathology and immune responses were studied. Plasma alanine and aspartate amino-transferase levels were significantly higher in Jα18(-/-) mice than in WT mice two days after CCl(4) administration. Chemokine CXCL1/keratinocyte-derived chemokine (KC) and MMP-8 were significantly higher in iNKT cell-deficient mice than in control mice. The more severe liver injury in Jα18(-/-) mice was associated with greater leukocyte infiltrate, which was enriched in neutrophils (CD11b(+) CD11c(-) Gr-1(+) cells), in agreement with CXCL1/KC and MMP-8 levels. Complementary experiments with NK-depleted animals indicate a minor role for NK cells in the liver damage found in iNKT-deficient mice. Thus, unlike for ConA-induced hepatitis, we report that iNKT cells protect the liver against acute hepatitis induced by CCl(4) and limit neutrophil infiltration.
Published: 2011

13. Langerin+ dendritic cells are responsible for LPS-induced reactivation of allergen-specific Th2 responses in postasthmatic mice

Author: Julie Cazareth, A Ortiz-Stern, Valérie Julia, David Dombrowicz, Akira Kanda, Anne Lazzari, Nicolas Glaichenhaus, Cyrille Mionnet, Sébastien Fleury, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Immunologie des maladies infectieuses allergiques et autoimmunes, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Université Lille Nord de France (COMUE), Institut de pharmacologie moléculaire et cellulaire (IPMC), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Lipopolysaccharides, Lipopolysaccharide, MESH: Asthma, Receptors, Antigen, T-Cell, alpha-beta, [SDV]Life Sciences [q-bio], Lymphocyte Activation, medicine.disease_cause, Mice, chemistry.chemical_compound, 0302 clinical medicine, Allergen, Cell Movement, Immunology and Allergy, MESH: Animals, Receptor, Lung, MESH: Cell Movement, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Mice, Inbred BALB C, 0303 health sciences, MESH: Receptors, Antigen, T-Cell, alpha-beta, biology, integumentary system, MESH: Dendritic Cells, respiratory system, 3. Good health, medicine.anatomical_structure, Antigens, Surface, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Cells, Cultured, MESH: Allergens, Langerin, Ovalbumin, MESH: Mice, Transgenic, MESH: Antigens, Surface, T cell, Immunology, MESH: Mice, Inbred BALB C, Mice, Transgenic, 03 medical and health sciences, Th2 Cells, Antigen, MESH: Eosinophils, MESH: Th2 Cells, MESH: Mannose-Binding Lectins, medicine, Animals, Humans, Lectins, C-Type, MESH: Lung, MESH: Lymphocyte Activation, MESH: Mice, 030304 developmental biology, MESH: Ovalbumin, MESH: Humans, Dendritic Cells, Allergens, Eosinophil, Asthma, respiratory tract diseases, Eosinophils, Mannose-Binding Lectins, chemistry, biology.protein, MESH: Lipopolysaccharides, MESH: Lectins, C-Type, 030215 immunology
Abstract: International audience; Allergic asthma is a T cell-dependent inflammatory lung disease that results from complex interactions between genetic predisposition and environmental factors, including exposure to lipopolysaccharide (LPS). In this study, we have shown that airway LPS exposure was sufficient to induce airway hyperreactivity (AHR) and eosinophil recruitment in mice that had previously experienced an acute episode of allergic asthma. LPS-induced disease reactivation depended on the activation of allergen-specific CD4(+) T cells by a subset of lung langerin(+) dendritic cells (DCs) that retained the allergen. Upon LPS exposure, migration of langerin(+) DCs from lungs to draining lymph nodes increased and LPS-exposed langerin(+) DCs instructed CD4(+) T cells toward a T helper (Th) 2 response. Selective depletion of langerin(+) DCs prevented LPS-induced eosinophil recruitment and T-cell activation, further demonstrating a critical role for langerin(+) DCs in disease reactivation. This finding provides a possible explanation for the subclinical worsening of asthmatics following exposure to low-dose LPS.
Published: 2011

14. Immunology: Egocentric pre-T-cell receptors

Author: Malissen, Bernard, Luche, Hervé, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Protein Structure, Tertiary, MESH: Humans, MESH: Receptors, Antigen, T-Cell, alpha-beta, MESH: T-Lymphocytes, MESH: Protein Multimerization, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Animals, MESH: Crystallography, X-Ray, MESH: Gene Rearrangement, T-Lymphocyte, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2010

15. TCR beta allelic exclusion in dynamical models of V(D)J recombination based on allele independence

Author: Sébastien Jaeger, Bastien Fernandez, Pierre Ferrier, Etienne Farcot, Salvatore Spicuglia, Marie Laure Bonnet, Modeling plant morphogenesis at different scales, from genes to phenotype (VIRTUAL PLANTS), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de la Recherche Agronomique (INRA)-Amélioration génétique et adaptation des plantes méditerranéennes et tropicales (UMR AGAP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Centre de Physique Théorique - UMR 6207 (CPT), Centre National de la Recherche Scientifique (CNRS)-Université de Toulon (UTLN)-Université de Provence - Aix-Marseille 1-Université de la Méditerranée - Aix-Marseille 2, Centre de Physique Théorique - UMR 7332 (CPT), Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro), Université de la Méditerranée - Aix-Marseille 2-Université de Provence - Aix-Marseille 1-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Dynamical modeling, MESH: Feedback, Physiological, Receptors, Antigen, T-Cell, alpha-beta, Immunoglobulin Variable Region, MESH: Immunoglobulin Variable Region, MESH: T-Lymphocyte Subsets, MESH: Mice, Knockout, Mice, 0302 clinical medicine, Models, T-Lymphocyte Subsets, Receptors, Immunology and Allergy, MESH: Animals, MESH: Molecular Dynamics Simulation, Genetics, Gene Rearrangement, alpha-beta, Feedback, Physiological, Mice, Knockout, Recombination, Genetic, 0303 health sciences, MESH: Receptors, Antigen, T-Cell, alpha-beta, V(D)J recombination, MESH: Gene Rearrangement, T-Lymphocyte, Markov Chains, Allelic exclusion, Immunological, Antigen, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunoglobulin Joining Region, MESH: Recombination, Genetic, Recombination, Antibody Diversity, Physiological, Knockout, Immunology, Locus (genetics), chemical and pharmacologic phenomena, MESH: Immunoglobulin Joining Region, Computational biology, Biology, Molecular Dynamics Simulation, Gene Rearrangement, T-Lymphocyte, MESH: Models, Immunological, Feedback, 03 medical and health sciences, Genetic, MESH: Markov Chains, Animals, Allele, MESH: Mice, Alleles, 030304 developmental biology, Markov chain, MESH: Alleles, T-cell receptor, Models, Immunological, MESH: Antibody Diversity, T-Cell, T-Lymphocyte, 030215 immunology
Abstract: Allelic exclusion represents a major aspect of TCRβ gene assembly by V(D)J recombination in developing T lymphocytes. Despite recent progress, its comprehension remains problematic when confronted with experimental data. Existing models fall short in terms of incorporating into a unique distribution all the cell subsets emerging from the TCRβ assembly process. To revise this issue, we propose dynamical, continuous-time Markov chain-based modeling whereby essential steps in the biological procedure (D-J and V-DJ rearrangements and feedback inhibition) evolve independently on the two TCRβ alleles in every single cell while displaying random modes of initiation and duration. By selecting parameters via fitting procedures, we demonstrate the capacity of the model to offer accurate fractions of all distinct TCRβ genotypes observed in studies using developing and mature T cells from wild-type or mutant mice. Selected parameters in turn afford relative duration for each given step, hence updating TCRβ recombination distinctive timings. Overall, our dynamical modeling integrating allele independence and noise in recombination and feedback-inhibition events illustrates how the combination of these ingredients alone may enforce allelic exclusion at the TCRβ locus.
Published: 2010

16. Killer cell immunoglobulin-like receptor expression induction on neonatal CD8(+) T cells in vitro and following congenital infection with Trypanosoma cruzi

Author: Veronique M. Braud, Emmanuel Hermann, Cristina Alonso-Vega, Faustino Torrico, Carine Truyens, Rudy Parrado, Yves Carlier, Aurélie Berthe, Laboratoire de Parasitologie, Faculté de Médecine, Université libre de Bruxelles (ULB), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Centro Universitario de Medicina Tropical/Laboratorio de Medicina, Universidad Mayor de San Simón [Cochabamba, Bolivie] (UMSS), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), and Université Nice Sophia Antipolis (1965 - 2019) (UNS)
Subjects: CD3 Complex, MESH: Antigens, CD3, Receptors, Antigen, T-Cell, alpha-beta, Killer-cell immunoglobulin-like receptor, MESH: T-Lymphocyte Subsets, CD8-Positive T-Lymphocytes, Infant, Newborn, Diseases, MESH: Antibodies, Monoclonal, Interleukin 21, 0302 clinical medicine, MESH: Pregnancy, Receptors, KIR, Pregnancy, T-Lymphocyte Subsets, immune system diseases, Immunology and Allergy, Cytotoxic T cell, Enzyme Inhibitors, DNA Modification Methylases, MESH: Antigens, CD, MESH: DNA Modification Methylases, 0303 health sciences, DNA methylation, MESH: Receptors, Antigen, T-Cell, alpha-beta, ZAP70, MESH: Infant, Newborn, Antibodies, Monoclonal, Receptors, KIR3DL1, hemic and immune systems, Fetal Blood, Natural killer T cell, MESH: CD8-Positive T-Lymphocytes, 3. Good health, Cell biology, MESH: NK Cell Lectin-Like Receptor Subfamily C, T-cell receptors, Receptors, KIR2DL3, MESH: Enzyme Inhibitors, Receptors, KIR2DL2, Receptors, KIR2DL1, embryonic structures, Azacitidine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, NK Cell Lectin-Like Receptor Subfamily C, MESH: Trypanosoma cruzi, medicine.drug, Interleukin 2, MESH: Immunophenotyping, Trypanosoma cruzi, Immunology, MESH: Azacitidine, chemical and pharmacologic phenomena, MESH: Infant, Newborn, Diseases, Biology, Decitabine, Major histocompatibility complex, MESH: Receptors, KIR3DL1, Immunophenotyping, 03 medical and health sciences, Antigens, CD, MESH: Receptors, KIR, medicine, otorhinolaryngologic diseases, Humans, Chagas Disease, MESH: Chagas Disease, MESH: Fetal Blood, 030304 developmental biology, MESH: Humans, Infant, Newborn, MESH: Receptors, KIR2DL3, MESH: Interleukin-2, Original Articles, MESH: Receptors, KIR2DL1, MESH: Receptors, KIR2DL2, killer-cell immunoglobulin-like receptors, biology.protein, interleukin-2, MESH: Female, CD8, 030215 immunology
Abstract: International audience; Major histocompatibility complex (MHC) class I-specific inhibitory natural killer receptors (iNKRs) are expressed by subsets of T cells but the mechanisms inducing their expression are poorly understood, particularly for killer-cell immunoglobulin-like receptors (KIRs). The iNKRs are virtually absent from the surface of cord blood T cells but we found that KIR expression could be induced upon interleukin-2 stimulation in vitro. In addition, KIR expression was enhanced after treatment with 5-aza-2'-deoxycytidine, suggesting a role for DNA methylation. In vivo induction of KIR expression on cord blood T cells was also observed during a human congenital infection with Trypanosoma cruzi which triggers activation of fetal CD8(+) T cells. These KIR(+) T cells had an effector and effector/memory phenotype suggesting that KIR expression was consecutive to the antigenic stimulation; however, KIR was not preferentially found on parasite-specific CD8(+) T cells secreting interferon-gamma upon in vitro restimulation with live T. cruzi. These findings show that KIR expression is likely regulated by epigenetic mechanisms that occur during the maturation process of cord blood T cells. Our data provide a molecular basis for the appearance of KIRs on T cells with age and they have implications for T-cell homeostasis and the regulation of T-cell-mediated immune responses.
Published: 2010

17. High diversity of the immune repertoire in humanized NOD.SCID.gamma c-/- mice

Author: Marodon, Gilles, Desjardins, Delphine, Mercey, Laetitia, Baillou, Claude, Parent, Pierric, Manuel, Manuarii, Caux, Christophe, Bellier, Bertrand, Pasqual, Nicolas, Klatzmann, David, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC), Biologie et thérapeutique des pathologies immunitaires (BTPI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Unité d'hémato-oncologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Systématique, adaptation, évolution (SAE), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Bioénergétique fondamentale et appliquée, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital des Enfants, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service de biothérapies [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Institut Necker Enfants-Malades (INEM) ( INEM - UM 111 (UMR 8253 / U1151) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Biologie et thérapeutique des pathologies immunitaires ( BTPI ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Systématique, adaptation, évolution ( SAE ), Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, MESH: Mice, Inbred NOD, MESH : Gene Rearrangement, beta-Chain T-Cell Antigen Receptor, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, MESH : Immunoglobulin Heavy Chains, MESH: Flow Cytometry, Hepacivirus, Mice, SCID, Polymerase Chain Reaction, MESH: Mice, Knockout, MESH : Hepacivirus, MESH: Animals, Newborn, Mice, Mice, Inbred NOD, MESH : Antigens, CD45, MESH : Female, MESH: Animals, MESH: Hepacivirus, Gene Rearrangement, beta-Chain T-Cell Antigen Receptor, MESH: Mice, SCID, MESH : Polymerase Chain Reaction, Mice, Knockout, Immunity, Cellular, MESH: Receptors, Antigen, T-Cell, alpha-beta, MESH : Animals, Newborn, Receptors, Antigen, T-Cell, gamma-delta, Flow Cytometry, MESH : Receptors, Antigen, T-Cell, gamma-delta, MESH : Receptors, Antigen, T-Cell, alpha-beta, MESH : Immunophenotyping, MESH: Immunization, Female, Immunoglobulin Heavy Chains, MESH: Immunoglobulin Heavy Chains, MESH: Immunophenotyping, MESH : Flow Cytometry, MESH : Male, [ SDV.IMM.IMM ] Life Sciences [q-bio]/Immunology/Immunotherapy, MESH: Antigens, CD45, Immunophenotyping, MESH: Immunity, Cellular, MESH: Receptors, Antigen, T-Cell, gamma-delta, MESH : Mice, Animals, Humans, MESH: Mice, MESH : T-Lymphocytes, MESH: Humans, MESH : Mice, Inbred NOD, MESH : Humans, MESH: Clone Cells, MESH : Clone Cells, MESH : Immunity, Cellular, MESH: Polymerase Chain Reaction, MESH : Immunization, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, MESH : Mice, SCID, MESH: Male, Clone Cells, MESH: T-Lymphocytes, Animals, Newborn, MESH : Mice, Knockout, Leukocyte Common Antigens, Immunization, MESH : Animals, MESH: Female, MESH: Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
Abstract: International audience; The diversity of the human immune repertoire and how it relates to a functional immune response has not yet been studied in detail in humanized NOD.SCID.gammac(-/-) immunodeficient mice. Here, we used a multiplex PCR on genomic DNA to quantify the combinatorial diversity of all possible V-J rearrangements at the TCR-beta chain and heavy chain Ig locus. We first show that the combinatorial diversity of the TCR-beta chain generated in the thymus was well preserved in the periphery, suggesting that human T cells were not vastly activated in mice, in agreement with phenotypic studies. We then show that the combinatorial diversity in NOD.SCID.gammac(-/-) mice reached 100% of human reference samples for both the TCR and the heavy chain of Ig. To document the functionality of this repertoire, we show that a detectable but weak HLA-restricted cellular immune response could be elicited in reconstituted mice after immunization with an adenoviral vector expressing HCV envelope glycoproteins. Altogether, our results suggest that humanized mice express a diversified repertoire and are able to mount antigen-specific immune responses.
Published: 2009

18. Stepwise development of MAIT cells in mouse and human

Author: Claire Soudais, Ivan C. Moura, Stéphane Cherif, Hélène Laude, Emmanuel Martin, Lucia Guerri, Cécile Toly, Livine Duban, Anne Devys, Florence Tilloy, Sylvain Latour, Virginie Premel, Gabriella Vera, Olivier Lantz, Emmanuel Treiner, Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Inserm U925, équipe avenir, Développement normal et pathologique des lymphocytes et signalisation, Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement Français du Sang [Nantes], Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by grants from INSERM, Action incitative (ACI) 'physiologie integrative,' Agence Nationale pour la Recherche (ANR), and Section Médicale de l'Institut Curie. The development of the 3C10 antibody was funded in part by Innate-Pharma (Marseille, France). OL is supported by la Ligue Contre le Cancer as an 'équipe labellisée.', Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Picardie Jules Verne ( UPJV ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Picardie Jules Verne ( UPJV ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Immunité et cancer (U932), and Autard, Delphine
Subjects: Adoptive cell transfer, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, MESH : Kruppel-Like Transcription Factors, MESH: T-Lymphocyte Subsets, MESH: Mice, Knockout, MESH: Histocompatibility Antigens Class I, Mice, 0302 clinical medicine, MESH : Child, T-Lymphocyte Subsets, MESH: Child, Cytotoxic T cell, Promyelocytic Leukemia Zinc Finger Protein, MESH: Animals, Biology (General), Child, Mice, Knockout, 0303 health sciences, B-Lymphocytes, MESH: Receptors, Antigen, T-Cell, alpha-beta, biology, MESH : Immunity, Mucosal, General Neuroscience, Natural killer T cell, Fetal Blood, MESH : Mice, Transgenic, Cell biology, MESH : Receptors, Antigen, T-Cell, alpha-beta, MESH : Histocompatibility Antigens Class I, MESH: Kruppel-Like Transcription Factors, Antibody, General Agricultural and Biological Sciences, Research Article, Genetically modified mouse, MESH: Mice, Transgenic, QH301-705.5, Immunology, Kruppel-Like Transcription Factors, Mice, Transgenic, Mucosal associated invariant T cell, Thymus Gland, Major histocompatibility complex, General Biochemistry, Genetics and Molecular Biology, MESH : B-Lymphocytes, Minor Histocompatibility Antigens, 03 medical and health sciences, MESH: B-Lymphocytes, MESH : Mice, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, MESH : Thymus Gland, MESH: Fetal Blood, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Immunity, Mucosal, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH : T-Lymphocytes, MESH : Fetal Blood, MESH: Humans, General Immunology and Microbiology, T-cell receptor, Histocompatibility Antigens Class I, MESH : Humans, MESH: Thymus Gland, MESH : Natural Killer T-Cells, MESH : T-Lymphocyte Subsets, Gastrointestinal Tract, MESH: T-Lymphocytes, MESH: Natural Killer T-Cells, MESH: Immunity, Mucosal, biology.protein, Natural Killer T-Cells, MESH : Mice, Knockout, MESH: Gastrointestinal Tract, MESH : Animals, MESH : Gastrointestinal Tract, 030215 immunology
Abstract: Mucosal-associated invariant T (MAIT) cells display two evolutionarily conserved features: an invariant T cell receptor (TCR)α (iTCRα) chain and restriction by the nonpolymorphic class Ib major histocompatibility complex (MHC) molecule, MHC-related molecule 1 (MR1). MR1 expression on thymus epithelial cells is not necessary for MAIT cell development but their accumulation in the gut requires MR1 expressing B cells and commensal flora. MAIT cell development is poorly known, as these cells have not been found in the thymus so far. Herein, complementary human and mouse experiments using an anti-humanVα7.2 antibody and MAIT cell-specific iTCRα and TCRβ transgenic mice in different genetic backgrounds show that MAIT cell development is a stepwise process, with an intra-thymic selection followed by peripheral expansion. Mouse MAIT cells are selected in an MR1-dependent manner both in fetal thymic organ culture and in double iTCRα and TCRβ transgenic RAG knockout mice. In the latter mice, MAIT cells do not expand in the periphery unless B cells are added back by adoptive transfer, showing that B cells are not required for the initial thymic selection step but for the peripheral accumulation. In humans, contrary to natural killer T (NKT) cells, MAIT cells display a naïve phenotype in the thymus as well as in cord blood where they are in low numbers. After birth, MAIT cells acquire a memory phenotype and expand dramatically, up to 1%–4% of blood T cells. Finally, in contrast with NKT cells, human MAIT cell development is independent of the molecular adaptor SAP. Interestingly, mouse MAIT cells display a naïve phenotype and do not express the ZBTB16 transcription factor, which, in contrast, is expressed by NKT cells and the memory human MAIT cells found in the periphery after birth. In conclusion, MAIT cells are selected by MR1 in the thymus on a non-B non-T hematopoietic cell, and acquire a memory phenotype and expand in the periphery in a process dependent both upon B cells and the bacterial flora. Thus, their development follows a unique pattern at the crossroad of NKT and γδ T cells., Author Summary White blood cells, or lymphocytes, play an important role in defending the body from infection and disease. T lymphocytes come in many varieties with diverse functions. Mucosal-associated invariant T (MAIT) cells constitute a subset of unconventional T lymphocytes, characterized by their invariant T cell receptor (TCR)α chain and their requirement for the nonpolymorphic class Ib (MHC) molecule, MR1. MAIT cells are extremely abundant in human blood and mucosae. Contrary to mainstream T cells, their development requires B cells and commensal microbial flora. To shed light on the little-understood MAIT cells, we used new tools, including an antibody that we recently developed to detect human MAIT cells, and we were able to show that MAIT cell development is a stepwise process, with an intra-thymic selection followed by peripheral expansion. We show that thymic selection is MR1 dependent but requires neither B cells nor the commensal flora, which are both necessary for the expansion in the periphery. In contrast with the other evolutionarily conserved invariant subset, the natural killer T (NKT) cells, we found that MAIT cells exit the thymus as “naïve” cells before becoming antigen-experienced memory cells and expanding in number to represent a significant 1%–4% of peripheral T cells in human blood. In mice, we found that MAIT cells remain naïve and do not expand substantially. We conclude that MAIT cell development follows a unique scheme, where, unlike NKT cells, MAIT cell selection and expansion are uncoupled events that are mediated by distinct cell types in different compartments., Mucosal-associated invariant T cells, the most abundant invariant T cell subset in humans, arise via a distinct developmental pathway that represents a hybrid of that seen for NKT and γδ T cells, two other unconventional T cell subsets.
Published: 2009

19. Immune constitution monitoring after PBMC transplantation in complete DiGeorge syndrome: an eight-year follow-up

Author: Nicolas Daguindau, Mylène Beri, Christophe Ferrand, Véronique Decot, Véronique Latger-Cannard, Danièle Bensoussan, Rosine Nzietchueng, Capucine Picard, Alexandra Salmon, Pierre Bordigoni, Marie José Gregoire, Jean-François Stoltz, Saas, Philippe, Unité de Thérapie cellulaire et Tissus, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université Henri Poincaré - Nancy 1 (UHP), Unité de Transplantation Médullaire, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Hôpital d'enfants, Laboratoire Énergies et Mécanique Théorique et Appliquée (LEMTA ), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Risque cardiovasculaire, rigidité-fibrose et hypercoagulabilité (RCV), Université Henri Poincaré - Nancy 1 (UHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre d'étude des Déficits Immunitaires, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie Biologique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Génétique [CHRU Nancy], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])
Subjects: Male, Receptors, Antigen, T-Cell, alpha-beta, CD8-Positive T-Lymphocytes, 0302 clinical medicine, DiGeorge syndrome, Immunology and Allergy, MESH: Monitoring, Immunologic, MESH: Chimera, MESH: Treatment Outcome, 0303 health sciences, MESH: Receptors, Antigen, T-Cell, alpha-beta, MESH: DNA, Telomere, MESH: CD8-Positive T-Lymphocytes, MESH: Infant, 3. Good health, MESH: Leukocytes, Mononuclear, Treatment Outcome, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Transplantation, Isogeneic, MESH: Lymphocyte Count, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, CD4-CD8 Ratio, Recent Thymic Emigrant, Thymus Gland, Biology, Peripheral blood mononuclear cell, 03 medical and health sciences, Chimera (genetics), Immune system, Monitoring, Immunologic, Immunity, DiGeorge Syndrome, medicine, Humans, Lymphocyte Count, 030304 developmental biology, MESH: Humans, MESH: DiGeorge Syndrome, Chimera, Infant, DNA, MESH: Thymus Gland, medicine.disease, MESH: Male, Transplantation, Transplantation, Isogeneic, Leukocytes, Mononuclear, MESH: CD4-CD8 Ratio, MESH: Telomere, CD8, 030215 immunology
Abstract: International audience; A young boy with a confirmed complete DiGeorge Syndrome (cDGS) underwent a peripheral blood mononuclear cell transplantation (PBMCT) from his HLA-identical sister at 4.5 years of age, without a conditioning regimen. Eight years later, he is healthy with good immunological functions in the presence of a stable mixed T-cell chimerism. Absence of recent thymic emigrants is confirmed. We observe an inverted CD4+/CD8+ ratio, related to the CD8 subset expansion, a skewing of the TCR repertoire, especially on the CD8+ subset and a telomere loss on the CD8+ cells compared to the donor. However, these anomalies do not seem to have an impact on functional immunity. PBMCT in cDGS using an HLA-matched sibling donor provides good long-lasting immunity and is an easy alternative to bone marrow transplantation and to thymic transplantation.
Published: 2008

20. Coronin-1A links cytoskeleton dynamics to TCR alpha beta-induced cell signaling

Author: Mugnier, Bénédicte, Nal, Béatrice, Verthuy, Christophe, Boyer, Claude, Lam, David, Chasson, Lionel, Nieoullon, Vincent, Chazal, Geneviève, Guo, Xiao-Jun, He, Hai-Tao, Rueff-Juy, Dominique, Alcover, Andrés, Ferrier, Pierre, Dumonceaud, Corinne, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie Cellulaire des Lymphocytes (BIOCELLY), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Développement et pathologie du motoneurone, Institut National de la Santé et de la Recherche Médicale (INSERM), Immunophysiopathologie Infectieuse, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)
Subjects: MESH: Signal Transduction, Cell Survival, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, Immunology, lcsh:Medicine, macromolecular substances, Lymphocyte Activation, MESH: Actins, MESH: Mice, Knockout, Mice, MESH: Microfilament Proteins, MESH: Cytoskeleton, Animals, Homeostasis, MESH: Animals, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], lcsh:Science, MESH: Lymphocyte Activation, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], MESH: Mice, Cytoskeleton, Mice, Knockout, MESH: Cytokines, MESH: Receptors, Antigen, T-Cell, alpha-beta, lcsh:R, Microfilament Proteins, Actins, MESH: T-Lymphocytes, MESH: Cell Survival, MESH: Homeostasis, Immunology/Leukocyte Activation, Cytokines, lcsh:Q, Immunology/Leukocyte Development, Signal Transduction, Research Article
Abstract: International audience; Actin polymerization plays a critical role in activated T lymphocytes both in regulating T cell receptor (TCR)-induced immunological synapse (IS) formation and signaling. Using gene targeting, we demonstrate that the hematopoietic specific, actin- and Arp2/3 complex-binding protein coronin-1A contributes to both processes. Coronin-1A-deficient mice specifically showed alterations in terminal development and the survival of alpha beta T cells, together with defects in cell activation and cytokine production following TCR triggering. The mutant T cells further displayed excessive accumulation yet reduced dynamics of F-actin and the WASP-Arp2/3 machinery at the IS, correlating with extended cell-cell contact. Cell signaling was also affected with the basal activation of the stress kinases sAPK/JNK1/2; and deficits in TCR-induced Ca2+ influx and phosphorylation and degradation of the inhibitor of NF-kappaB (I kappa B). Coronin-1A therefore links cytoskeleton plasticity with the functioning of discrete TCR signaling components. This function may be required to adjust TCR responses to selecting ligands accounting in part for the homeostasis defect that impacts alpha beta T cells in coronin-1A deficient mice, with the exclusion of other lympho/hematopoietic lineages.
Published: 2008

21. Clinical spectrum of gammadelta+ T cell LGL leukemia: analysis of 20 cases

Author: A S, Bourgault-Rouxel, T P, Loughran, R, Zambello, P K, Epling-Burnette, G, Semenzato, J, Donadieu, L, Amiot, T, Fest, T, Lamy, Service d'hématologie clinique, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Department of Experimental Immunology, University of Medicine, Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Hématologie, Immunologie et de Thérapie Cellulaire (HITC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Microenvironnement et cancer (MiCa), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), National Institute of Health, Université de Rennes (UR)-Hôpital Pontchaillou, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Adult, Male, LGL leukemia, Leukemia, T-Cell, MESH: Immunophenotyping, Receptors, Antigen, T-Cell, alpha-beta, chemical and pharmacologic phenomena, MESH: Leukopenia, Autoimmune Diseases, Immunophenotyping, MESH: Aged, 80 and over, MESH: Receptors, Antigen, T-Cell, gamma-delta, TCRγδ, TCRαβ, MESH: Autoimmune Diseases, Humans, Aged, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, MESH: Receptors, Antigen, T-Cell, alpha-beta, MESH: Humans, Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor, MESH: Clone Cells, Receptors, Antigen, T-Cell, gamma-delta, hemic and immune systems, MESH: Adult, Leukopenia, Middle Aged, MESH: Male, Clone Cells, MESH: Splenomegaly, stomatognathic diseases, MESH: Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Splenomegaly, Female, MESH: Female, MESH: Leukemia, T-Cell
Abstract: International audience; We report on the clinico-biological characteristics of 20 cases of gammadelta T cell large granular lymphocyte (LGL) leukemia. All the data were compared to that of 196 cases with alphabeta T cell subtype, which represents the majority of T cell LGL leukemias. Clinical findings were quite similar in the two groups regarding age, sex ratio, recurrent infections, and association with auto-immune diseases especially rheumatoid arthritis. Gammadelta LGL predominantly expressed a CD3+/CD4-/CD8+/CD16+/CD57+ phenotype, in 50% of cases. Clinical outcome was favorable for these patients with overall survival of 85% at 3 years. Fifty percent of gammadelta patients required treatment and the response to therapy was estimated at 55%. gammadelta and alphabeta T cell LGL leukemia harbor a very similar clinico-biological behavior and represent part of an antigen-driven T cell lymphoproliferation.
Published: 2008

22. Replication of ICP0-Null Mutant Herpes Simplex Virus Type 1 Is Restricted by both PML and Sp100▿

Author: Philippe Gripon, Roger D. Everett, Anne Orr, Carlos Parada, Hüseyin Sirma, MRC Virology Unit, Institute of Virology, Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes (UR), Régulations des équilibres fonctionnels du foie normal et pathologique, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Heinriche-Pette-Institute, the DFG, Stiftung für neurovirale Erkrankungen to H.S, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MESH: Neoplasm Proteins, viruses, Mutant, Fluorescent Antibody Technique, Gene Expression, Herpesvirus 1, Human, Viral Plaque Assay, MESH: Leukopenia, MESH: Base Sequence, Promyelocytic Leukemia Protein, Virus Replication, Autoantigens, MESH: Aged, 80 and over, MESH: Autoimmune Diseases, Gene expression, MESH: Microscopy, Confocal, Nuclear protein, MESH: Fluorescent Antibody Technique, MESH: Aged, 0303 health sciences, MESH: Middle Aged, MESH: Receptors, Antigen, T-Cell, alpha-beta, Microscopy, Confocal, biology, 030302 biochemistry & molecular biology, Nuclear Proteins, Antigens, Nuclear, MESH: Transcription Factors, MESH: Splenomegaly, 3. Good health, Ubiquitin ligase, Virus-Cell Interactions, Neoplasm Proteins, MESH: Herpesvirus 1, Human, MESH: Viral Plaque Assay, MESH: Autoantigens, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Histone deacetylase activity, MESH: Leukemia, T-Cell, medicine.drug, MESH: DNA Primers, MESH: Gene Expression, MESH: Mutation, MESH: Immunophenotyping, Ubiquitin-Protein Ligases, Immunology, Microbiology, Immediate early protein, Cell Line, Immediate-Early Proteins, 03 medical and health sciences, Promyelocytic leukemia protein, MESH: Receptors, Antigen, T-Cell, gamma-delta, Virology, medicine, Humans, MESH: Tumor Suppressor Proteins, MESH: Antigens, Nuclear, 030304 developmental biology, DNA Primers, MESH: Humans, Base Sequence, Tumor Suppressor Proteins, MESH: Virus Replication, MESH: Clone Cells, MESH: Adult, MESH: Immediate-Early Proteins, biochemical phenomena, metabolism, and nutrition, MESH: Ubiquitin-Protein Ligases, Molecular biology, MESH: Male, MESH: Cell Line, MESH: Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor, Trichostatin A, Insect Science, Mutation, biology.protein, MESH: Nuclear Proteins, MESH: Female, Transcription Factors
Abstract: Herpes simplex virus type 1 (HSV-1) mutants that fail to express the viral immediate-early protein ICP0 have a pronounced defect in viral gene expression and plaque formation in limited-passage human fibroblasts. ICP0 is a RING finger E3 ubiquitin ligase that induces the degradation of several cellular proteins. PML, the organizer of cellular nuclear substructures known as PML nuclear bodies or ND10, is one of the most notable proteins that is targeted by ICP0. Depletion of PML from human fibroblasts increases ICP0-null mutant HSV-1 gene expression, but not to wild-type levels. In this study, we report that depletion of Sp100, another major ND10 protein, results in a similar increase in ICP0-null mutant gene expression and that simultaneous depletion of both proteins complements the mutant virus to a greater degree. Although chromatin assembly and modification undoubtedly play major roles in the regulation of HSV-1 infection, we found that inhibition of histone deacetylase activity with trichostatin A was unable to complement the defect of ICP0-null mutant HSV-1 in either normal or PML-depleted human fibroblasts. These data lend further weight to the hypothesis that ND10 play an important role in the regulation of HSV-1 gene expression.
Published: 2007

23. Analysis of the TCR alpha-chain rearrangement profile in human T lymphocytes

Author: Patrizia Fuschiotti, Evelyne Jouvin-Marche, Jacqueline London, Vivien Hierle, Eve Borel, Patrice N. Marche, Nicolas Pasqual, Contrôle moléculaire de la réponse immune specifique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF), Modèles de dérégulation génique : trisomie 21 et hyperhomocystéinémie (EA_3508), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Agence Nationale de Recherches sur le SIDA (France). P.F. was 'Chercheur Associée' at the CNRS, N.P. is a recipient of an INSERM-CEA fellowship., Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Marche, Patrice
Subjects: Male, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, MESH: Genetic Markers, Valpha repertoire, Genetic recombination, 0302 clinical medicine, Conserved Sequence, Recombination, Genetic, Genetics, 0303 health sciences, MESH: Conserved Sequence, MESH: Receptors, Antigen, T-Cell, alpha-beta, MESH: Middle Aged, Gene rearrangement, Repertoire, MESH: Infant, Newborn, Middle Aged, MESH: Infant, medicine.anatomical_structure, MESH: Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Recombination, Genetic, Human, Adult, Genetic Markers, TCRAD locus, [SDV.IMM] Life Sciences [q-bio]/Immunology, Pseudogene, T cell, Immunology, Locus (genetics), Thymus Gland, Biology, 03 medical and health sciences, medicine, Humans, Molecular Biology, Gene, 030304 developmental biology, MESH: Humans, T-cell receptor, Infant, Newborn, Infant, MESH: Adult, MESH: Thymus Gland, MESH: Male, MESH: T-Lymphocytes, Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor, MESH: Female, TCR alpha diversity, 030215 immunology
Abstract: doi : 10.1016/j.molimm.2007.02.017; International audience; The size of the available human alphabeta T cell repertoire is difficult to determine and is open to debate. Empirical analysis of TCR beta-chain diversity reveals approximately 10(6) different beta chains in peripheral blood. Due in part to locus complexity, comparable information for TCR alpha is lacking. Rather, current estimates for human TCR alpha diversity, and hence, total repertoire diversity, are based on theoretical analyses that assume equal probabilities of rearrangement between any V alpha gene and J alpha gene. Here, we report on a systematic locus-wide rearrangement analysis of the TCR alpha-chain in human T cells. We first demonstrate that the V-J alpha recombination in the thymus is not random but depends on the reciprocal V alpha and J alpha position within the locus. Characterization of the frequency of gene usage combined with identification of five previously unrecognized pseudogenes enables us to empirically estimate the human TCR alpha combinatorial repertoire. The number of V-J alpha combinations achieved is approximately 44-56% of the total combinatorial possibilities, significantly lower than theoretical estimates. We also demonstrate that TCR alpha-chain diversity in peripheral T lymphocytes mimics the same general patterns of rearrangement as observed in the thymus, and these patterns appear conserved among different individuals. This unexpected observation indicates that, unlike the TCR beta locus, the human TCR alpha-chain repertoire is primarily predetermined by genetic recombination and its size is restricted by limits on the combinatorial repertoire rather than post-thymic selection.
Published: 2007

24. Peripheral T cell lymphopenia and concomitant enrichment in naturally arising regulatory T cells: the case of the pre-Talpha gene-deleted mouse

Author: Rhodri Ceredig, Fabien Agenès, Nabil Bosco, Antonius G. Rolink, Contrôle moléculaire de la réponse immune specifique, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Developmental and Molecular Immunology, Department of Clinical and Biological Sciences (DKBW), University of Basel (Unibas), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Saas, Philippe, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC)
Subjects: medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Parabiosis, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, T cell, Immunology, Thymus Gland, MESH: T-Lymphocyte Subsets, Biology, T-Lymphocytes, Regulatory, MESH: Mice, Knockout, MESH: Lymphopenia, Mice, T-Lymphocyte Subsets, Lymphopenia, Internal medicine, medicine, Animals, Immunology and Allergy, MESH: Animals, IL-2 receptor, MESH: Bone Marrow Transplantation, MESH: Mice, Bone Marrow Transplantation, Mice, Knockout, Transplantation Chimera, MESH: Receptors, Antigen, T-Cell, alpha-beta, MESH: T-Lymphocytes, Regulatory, FOXP3, MESH: Thymus Gland, Phenotype, Molecular biology, Thymocyte, Lymphatic system, medicine.anatomical_structure, Endocrinology, MESH: T-Lymphocytes, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Parabiosis, CD8, MESH: Transplantation Chimera
Abstract: In pre-Tα (pTα) gene-deleted mice, the positively selectable CD4+CD8+ double-positive thymocyte pool is only 1% that in wild-type mice. Consequently, their peripheral T cell compartment is severely lymphopenic with a concomitant increase in proportion of CD25+FoxP3+ regulatory T cells. Using mixed bone marrow chimeras, where thymic output was 1% normal, the pTα−/− peripheral T cell phenotype could be reproduced with normal cells. In the pTα−/− thymus and peripheral lymphoid organs, FoxP3+CD4+ cells were enriched. Parabiosis experiments showed that many pTα−/−CD4+ single-positive thymocytes represented recirculating peripheral T cells. Therefore, the enrichment of FoxP3+CD4+ single-positive thymocytes was not solely due to increased thymic production. Thus, the pTα−/− mouse serves as a model system with which to study the consequences of chronic decreased thymic T cell production on the physiology of the peripheral T cell compartment.
Published: 2006

25. Human articular chondrocytes suppress in vitro proliferation of anti-CD3 activated peripheral blood mononuclear cells

Author: Alan Tyndall, Andrea Barbero, Christian Candrian, Ivan Martin, Chiara Bocelli-Tyndall, Rhodri Ceredig, Department of Rheumatology, University of Basel (Unibas), Department of Biomedicine [Basel], University Hospital Basel [Basel], Developmental and Molecular Immunology, Department of Clinical and Biological Sciences (DKBW), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Saas, Philippe, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: Cartilage, Articular, Male, Platelet-derived growth factor, CD3 Complex, Physiology, MESH: Antigens, CD3, Clinical Biochemistry, MESH: T-Lymphocyte Subsets, Fibroblast growth factor, MESH: Mice, Knockout, MESH: Hematopoietic Stem Cells, chemistry.chemical_compound, 0302 clinical medicine, MESH: Animals, MESH: Bone Marrow Transplantation, MESH: Antigens, CD, 0303 health sciences, MESH: Receptors, Antigen, T-Cell, alpha-beta, MESH: Middle Aged, biology, MESH: Bone Marrow Cells, Middle Aged, MESH: Leukocytes, Mononuclear, medicine.anatomical_structure, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Parabiosis, Platelet-derived growth factor receptor, MESH: Transplantation Chimera, MESH: Cell Differentiation, Adult, Stromal cell, [SDV.IMM] Life Sciences [q-bio]/Immunology, Bone Marrow Cells, Peripheral blood mononuclear cell, Antibodies, MESH: Lymphopenia, 03 medical and health sciences, Chondrocytes, MESH: B-Lymphocytes, MESH: Chondrocytes, MESH: Cell Proliferation, medicine, MESH: Cell Shape, Humans, MESH: Mice, Cell Shape, 030304 developmental biology, Cell Proliferation, MESH: Humans, MESH: T-Lymphocytes, Regulatory, MESH: Antibodies, Mesenchymal stem cell, MESH: Adult, Cell Biology, MESH: Thymus Gland, Molecular biology, MESH: Male, MESH: T-Lymphocytes, chemistry, Immunology, MESH: Cartilage, Articular, biology.protein, Leukocytes, Mononuclear, Bone marrow, MESH: Stromal Cells, Stromal Cells, 030215 immunology, Transforming growth factor
Abstract: International audience; OBJECTIVE: To investigate whether mature human articular chondrocytes (AC) exhibit an antiproliferative effect on activated peripheral blood mononuclear cells (PBMC) and to compare this effect with other cells of mesenchymal origin. METHODS: AC from healthy cadaveric cartilage were grown for different passages, in the absence (control) or presence of factors enhancing cell de-differentiation (transforming growth factor (TGF)beta1, fibroblast growth factor (FGF)-2, and platelet derived growth factor (PDGF)bb-TFP medium). Cell ability to suppress PBMC proliferation driven by anti-CD3 antibody was measured by tritiated thymidine uptake following incubation for 48 h at different PBMC:AC ratios and expressed as percent of residual proliferation (RP). AC antiproliferative effect was compared to that of control dermal fibroblasts (DF) and bone marrow stromal cells (BMSC). RESULTS: AC exhibited a cell number-dependent antiproliferative effect. The strongest effect (up to 2% RP) was measured using the least expanded AC cultures. The use of TFP medium for AC expansion resulted in a significantly lower antiproliferative effect, in the range of that induced by BMSC (up to 18% RP). Also DF induced a marked antiproliferative effect (up to 11% RP). CONCLUSION: We report for the first time that human AC have a marked antiproliferative effect on anti-CD3 stimulated PBMC, which is reduced upon culture in medium-inducing extensive cell de-differentiation. These results reflect the immunosuppressive properties observed for other different mesenchymal cell types and raise the question of a potential common physiological role in local tissue protection.
Published: 2006

26. Overexpression of cellular prion protein induces an antioxidant environment altering T cell development in the thymus

Author: Jouvin-Marche, Evelyne, Attuil-Audenis, Valérie, Aude-Garcia, Catherine, Rachidi, Walid, Zabel, Mark, Podevin-Dimster, Valérie, Siret, Carole, Huber, Christoph, Martinic, Marianne, Riondel, Jacqueline, Villiers, Christian, Favier, Alain, Naquet, Philippe, Cesbron, Jean-Yves, Marche, Patrice, Contrôle moléculaire de la réponse immune specifique, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de biologie du stress oxydant, Université Joseph Fourier - Grenoble 1 (UJF), Neuropathology institute, University hospital of Zurich [Zurich], Transmission et pathogénèse des maladies à prions (TPMP), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institute of experimental immunology, grants from the Groupement d'Inte´reˆt Scientifique- Prion (Grants A42 and A108), the Commissariat a` l'Energie Atomique Tox- Nuc Program (Grant 13-10), and the European Union, Project Number QLK5-CT- 2002-01044. V.A.-A. is a recipient of a GIS-Prion Fellowship., and Marche, Patrice
Subjects: MESH: Cell Differentiation, MESH: Receptors, Antigen, T-Cell, alpha-beta, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Mice, Transgenic, Oxydative Stress, MESH: Antioxidants, MESH: Dietary Supplements, MESH: Thymus Gland, MESH: Phenotype, MESH: Gene Expression Regulation, Thymus, MESH: Copper, MESH: Prions, MESH: T-Lymphocytes, MESH: Mice, Inbred C57BL, Prion, T lymphocyte, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Animals, MESH: Antigens, CD, MESH: Mice
Abstract: E.J.-M, V.A.-A. and C.A.-G. contributed equally to this work.; International audience; Cellular prion protein (PrP(C)) is an ubiquitously expressed glycoprotein whose roles are still widely discussed, particularly in the field of immunology. Using TgA20- and Tg33-transgenic mice overexpressing PrP(C), we investigated the consequences of this overexpression on T cell development. In both models, overexpression of PrP(C) induces strong alterations at different steps of T cell maturation. On TgA20 mice, we observed that these alterations are cell autonomous and lead to a decrease of alphabeta T cells and a concomitant increase of gammadelta T cell numbers. PrP(C) has been shown to bind and chelate copper and, interestingly, under a copper supplementation diet, TgA20 mice presented a partial restoration of the alphabeta T cell development, suggesting that PrP(C) overexpression, by chelating copper, generates an antioxidant context differentially impacting on alphabeta and gammadelta T cell lineage.
Published: 2006

27. Overexpression of cellular prion protein induces an antioxidant environment altering T cell development in the thymus

Author: Jacqueline Riondel, Jean-Yves Cesbron, Marianne M. A. Martinic, Valérie Attuil-Audenis, Catherine Aude-Garcia, Alain Favier, Carole Siret, Patrice N. Marche, Evelyne Jouvin-Marche, Christian L. Villiers, Christoph Huber, Philippe Naquet, Valérie Podevin-Dimster, Walid Rachidi, Mark D. Zabel, Contrôle moléculaire de la réponse immune specifique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire de biologie du stress oxydant, Université Joseph Fourier - Grenoble 1 (UJF), Neuropathology institute, University hospital of Zurich [Zurich], Transmission et pathogénèse des maladies à prions (TPMP), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institute of experimental immunology, grants from the Groupement d'Inte´reˆt Scientifique- Prion (Grants A42 and A108), the Commissariat a` l'Energie Atomique Tox- Nuc Program (Grant 13-10), and the European Union, Project Number QLK5-CT- 2002-01044. V.A.-A. is a recipient of a GIS-Prion Fellowship., Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cellular differentiation, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, MESH: Dietary Supplements, Antioxidants, Mice, 0302 clinical medicine, T lymphocyte, Immunology and Allergy, MESH: Animals, Receptor, MESH: Antigens, CD, Regulation of gene expression, 0303 health sciences, MESH: Receptors, Antigen, T-Cell, alpha-beta, Cell Differentiation, MESH: Gene Expression Regulation, Thymus, MESH: Copper, medicine.anatomical_structure, Phenotype, Prion, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Cell Differentiation, MESH: Mice, Transgenic, Prions, Transgene, T cell, Oxydative Stress, Immunology, Context (language use), Mice, Transgenic, Thymus Gland, Biology, MESH: Phenotype, 03 medical and health sciences, MESH: Prions, Antigen, MESH: Mice, Inbred C57BL, Antigens, CD, medicine, Animals, MESH: Mice, 030304 developmental biology, MESH: Antioxidants, MESH: Thymus Gland, Molecular biology, Mice, Inbred C57BL, MESH: T-Lymphocytes, Gene Expression Regulation, Dietary Supplements, 030217 neurology & neurosurgery, Copper
Abstract: E.J.-M, V.A.-A. and C.A.-G. contributed equally to this work.; International audience; Cellular prion protein (PrP(C)) is an ubiquitously expressed glycoprotein whose roles are still widely discussed, particularly in the field of immunology. Using TgA20- and Tg33-transgenic mice overexpressing PrP(C), we investigated the consequences of this overexpression on T cell development. In both models, overexpression of PrP(C) induces strong alterations at different steps of T cell maturation. On TgA20 mice, we observed that these alterations are cell autonomous and lead to a decrease of alphabeta T cells and a concomitant increase of gammadelta T cell numbers. PrP(C) has been shown to bind and chelate copper and, interestingly, under a copper supplementation diet, TgA20 mice presented a partial restoration of the alphabeta T cell development, suggesting that PrP(C) overexpression, by chelating copper, generates an antioxidant context differentially impacting on alphabeta and gammadelta T cell lineage.
Published: 2006

28. TCRgamma silencing during alphabeta T cell development depends upon pre-TCR-induced proliferation

Author: Ferrero, Isabel, Mancini, Stéphane J C, Grosjean, Frederic, Wilson, Anne, Otten, Luc, MacDonald, H Robson, Haon, Marie Laure, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)
Subjects: CD3 Complex, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Antigens, CD3, Receptors, Antigen, T-Cell, alpha-beta, chemical and pharmacologic phenomena, Thymus Gland, MESH: T-Lymphocyte Subsets, Antibodies, Mice, T-Lymphocyte Subsets, MESH: Receptors, Antigen, T-Cell, gamma-delta, MESH: Cell Proliferation, Silencer Elements, Transcriptional, Animals, Cell Lineage, MESH: Animals, MESH: Gene Silencing, Gene Silencing, MESH: Mice, Cell Proliferation, MESH: Receptors, Antigen, T-Cell, alpha-beta, MESH: Antibodies, Receptors, Antigen, T-Cell, gamma-delta, hemic and immune systems, MESH: Thymus Gland, MESH: Cell Lineage, stomatognathic diseases, MESH: Silencer Elements, Transcriptional, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract: During thymus development, immature T cells become committed to two distinct lineages based upon expression of alphabeta or gammadelta TCR. In the alphabeta lineage, developing thymocytes progressively extinguish transcription of the TCRgamma genes by a poorly understood process known as gamma silencing. We show that alphabeta lineage thymocytes in mice lacking a functional pre-TCR undergo limited proliferation and fail to silence TCRgamma genes during development. Stimulation of pre-TCR-deficient immature thymocytes with anti-CD3 Abs does not directly down-regulate TCRgamma transcription but restores TCRgamma silencing following proliferation. Collectively our data reveal an important role for pre-TCR induced proliferation in activating the TCRgamma silencer in alphabeta lineage thymocytes, a process that may reinforce alphabeta or gammadelta lineage commitment.
Published: 2006

29. Isolation of Regulatory T Cells in the Skin of a Human Hand-Allograft, Up to Six Years Posttransplantation

Author: Lionel Badet, Pierre Tiberghien, Christophe Ferrand, Jean-Michel Dubernard, Emmanuel Morelon, Annie Farre, Muriel Dubosson, Palmina Petruzzo, Pierre Miossec, Xavier Martin, Valérie Dubois, Jean Kanitakis, Assia Eljaafari, Department of Immunogenomics, Mixed Unit HCL-BioMerieux, Hopital E. Herriot, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Department of Dermatology, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), HLA Department, EFS Rhone-Alpes, Department of Transplantation Surgery, Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ElJaafari, Assia, Saas, Philippe, Department of Transplantation Medicine, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Pathology, MESH: Interleukin-10, medicine.medical_treatment, Receptors, Antigen, T-Cell, alpha-beta, [SDV]Life Sciences [q-bio], MESH: Membrane Glycoproteins, 030230 surgery, T-Lymphocytes, Regulatory, 0302 clinical medicine, Transforming Growth Factor beta, ComputingMilieux_MISCELLANEOUS, Skin, Membrane Glycoproteins, MESH: Receptors, Antigen, T-Cell, alpha-beta, MESH: Pore Forming Cytotoxic Proteins, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, medicine.diagnostic_test, Graft Survival, FOXP3, Forkhead Transcription Factors, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, 3. Good health, Interleukin-10, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, [SDV.IMM]Life Sciences [q-bio]/Immunology, Adult, Pore Forming Cytotoxic Proteins, medicine.medical_specialty, MESH: Graft Survival, [SDV.IMM] Life Sciences [q-bio]/Immunology, T cell, Hand Transplantation, chemical and pharmacologic phenomena, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Peripheral blood mononuclear cell, MESH: Hand, 03 medical and health sciences, Immune system, MESH: Skin, MESH: Forkhead Transcription Factors, Biopsy, medicine, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, RNA, Messenger, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Transforming Growth Factor beta, MESH: RNA, Messenger, Transplantation, MESH: Humans, business.industry, Perforin, MESH: T-Lymphocytes, Regulatory, MESH: Adult, T lymphocyte, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, MESH: Perforin, biology.protein, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, 030215 immunology, Allotransplantation
Abstract: International audience; BACKGROUND: A bilateral hand allotransplantation was performed in a patient six years ago. Whereas skin is known to be highly immunogenic, grafts have been well accepted up to now. Therefore, here we investigated the putative presence of regulatory T cells in the graft. METHODS: Skin biopsies were performed at different time points and analyzed by immunochemistry. T cells were initially expanded with interleukin (IL)-2. In the latter biopsy, skin was directly analyzed by reverse-transcriptase polymerase chain reaction without any culture. RESULTS: When tested against donor mononuclear cells, donor-primed skin T cells demonstrated unresponsiveness and inhibited donor-directed blood T cell alloresponse. Moreover, their T-cell receptor-Vbeta repertoire was skewed, in contrast to that of peripheral blood T cells. Retrospectively, nuclear FoxP3 expression in skin was measured by immunohistochemistry and was found positive at that time, but appeared to increase with time. This result was supported by the measurement of FoxP3 messenger RNA (mRNA) expression in the latter fresh biopsy, which showed higher levels than that of blood, together with no expression of perforin mRNA, but increased expression of transforming growth factor-beta and IL-10. No FoxP3 mRNA expression was found in the contralateral leg, due to the absence of T cell infiltrate. CONCLUSION: This study shows the presence of the FoxP3 marker, in a well accepted human composite tissue allograft, up to six years posttransplantation. Because a suppressive cytokinic profile was also detected intragraft, in the absence of perforin mRNA expression, our data suggest that regulatory T cells could play a role in the long-term survival of this allograft.
Published: 2006

30. Mechanisms of the natural reactivity of lymphocytes from noninfected individuals to membrane-associated Leishmania infantum antigens

Author: Dhafer Laouini, Beya Larguèche-Darwaz, Koussay Dellagi, Adrien Six, A. Sassi, Alexis Collette, Pierre André Cazenave, Laboratoire d'Immunopathologie, Vaccinologie et Génétique Moléculaire (LVGM), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Immunophysiopathologie Infectieuse, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), This work received financial support from the Tunisian State Secretariate for Research and Technology, and Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]
Subjects: CD4-Positive T-Lymphocytes, Receptors, Antigen, T-Cell, alpha-beta, [SDV]Life Sciences [q-bio], Lymphocyte Activation, MESH: Monocytes, Monocytes, 0302 clinical medicine, MESH: Child, Superantigen, Immunology and Allergy, MESH: Animals, Lymphocytes, Leishmania infantum, Child, 0303 health sciences, Antigen Presentation, MESH: Cytokines, MESH: Receptors, Antigen, T-Cell, alpha-beta, MESH: Infant, Newborn, MESH: CD4-Positive T-Lymphocytes, Natural killer T cell, Fetal Blood, MESH: Leishmania infantum, medicine.anatomical_structure, Phenotype, Child, Preschool, Antigens, Surface, Cytokines, Leishmaniasis, Visceral, MESH: Immunity, Innate, Adult, MESH: Antigens, Surface, T cell, CD3, Immunology, Antigen presentation, education, Antigens, Protozoan, Biology, In Vitro Techniques, MESH: Phenotype, 03 medical and health sciences, Antigen, medicine, Animals, Humans, MESH: Fetal Blood, MESH: Lymphocyte Activation, 030304 developmental biology, MESH: Humans, T-cell receptor, MESH: Child, Preschool, Histocompatibility Antigens Class II, Infant, Newborn, MESH: Adult, biology.organism_classification, Molecular biology, Immunity, Innate, MESH: Leishmaniasis, Visceral, MESH: Antigen Presentation, biology.protein, MESH: Histocompatibility Antigens Class II, MESH: Lymphocytes, 030215 immunology, MESH: Antigens, Protozoan
Abstract: Membrane-associated Leishmania Ags (MLA) or soluble Leishmania Ags were used in vitro to stimulate cord blood or PBMC from healthy donors noninfected by Leishmania parasites. MLA, but not soluble Leishmania Ags, constantly induce strong proliferation of cord blood mononuclear cells and PBMC from noninfected individuals. Responding cells are CD3+, CD4+, TCRαβ+, CD45RO+, and CD45RA+ and secrete IFN-γ and IL-10, but not IL-4. MLA do not activate NK cells nor NKT cells. Membrane Ags also induce purified macrophages from noninfected individuals to secrete IL-10 and TNF-α, but have no effect on IL-1α or IL-12 secretion. The effects of MLA are proteinase K-sensitive and resistant to lipid extraction. The lymphoproliferative responses are inhibited by anti-HLA-DR Abs and require Ag processing by APCs, excluding that the biological effect of MLA could be attributed to a superantigen. Finally, TCR repertoire analysis shows that the T cell expansion induced by MLA uses TCR with various variable β segment rearrangements and CDR3 lengths, features much more characteristic to those observed with a polyclonal activator than with a conventional Ag. These results suggest a particular mechanism developed during the host’s natural response to Leishmania parasites that allows direct activation of naive CD4 lymphocytes by parasite membrane-associated Ags.
Published: 2005

31. Repression of transcription at the human T-cell receptor Vbeta2.2 segment is mediated by a MAX/MAD/mSin3 complex acting as a scaffold for HDAC activity

Author: Virginie Brenac, François Sigaux, Malcolm Buckle, Myriam Cubizolles, M. P. Font, Lucien Cazes, Hervé Dombret, Lymphocyte et cancer, IFR105-Institut National de la Santé et de la Recherche Médicale (INSERM), Ciphergen, Ciphergen Biosystems, Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), and École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Transcription, Genetic, Receptors, Antigen, T-Cell, alpha-beta, Biophysics, Down-Regulation, Biochemistry, Jurkat cells, Histone Deacetylases, MESH: Down-Regulation, Jurkat Cells, 03 medical and health sciences, 0302 clinical medicine, Transcription (biology), MESH: Jurkat Cells, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Promoter Regions, Genetic, Receptor, Molecular Biology, Psychological repression, 030304 developmental biology, 0303 health sciences, MESH: Humans, MESH: Receptors, Antigen, T-Cell, alpha-beta, biology, Cell growth, Chemistry, MESH: Transcription, Genetic, T-cell receptor, Cell Biology, Molecular biology, MESH: Gene Expression Regulation, Cell biology, DNA-Binding Proteins, Repressor Proteins, MESH: Histone Deacetylases, MESH: Promoter Regions (Genetics), Histone, Gene Expression Regulation, MESH: Repressor Proteins, biology.protein, 030217 neurology & neurosurgery, MESH: DNA-Binding Proteins, Deacetylase activity
Abstract: The identification of protein components in complex networks of co-regulators responsible for the modulation of proliferation versus differentiation modes of cell growth is a major problem. We use a combination of surface enhanced laser desorption/ionization mass spectrometry, surface plasmon resonance coupled to electrospray mass spectrometry, and immunoelectromobility shift assays to identify members of the MAX/MAD family binding to a specific DNA silencer fragment involved in the regulation of transcription for the human T-cell receptor Vbeta2.2 segment. We also identify the cofactors mSin3 and N-CoR known to interact with histone deacetylases. Inhibition of deacetylase activity in Jurkat cells prevented transcription inhibitor complex formation at the Vbeta2.2 segment, suggesting that this is either directly or indirectly dependent on the presence of HDACs.
Published: 2004

32. The TL MHC class Ib molecule has only marginal effects on the activation, survival and trafficking of mouse small intestinal intraepithelial lymphocytes

Author: Jack R. Bennink, Jonathan W. Yewdell, Brian L. Kelsall, Sylvie Darche, Nathalie Pardigon, National Institutes of Health [Bethesda] (NIH), and We thank Drs D. Guy-Grand, D. Buzzoni-Gatel and L. Gapin for insightful discussions. Reovirus-infected animals were kindly provided by Dr M. Fleeton.
Subjects: MESH: Intestine, Small, Receptors, Antigen, T-Cell, alpha-beta, MESH: Membrane Glycoproteins, MESH: Interleukin-15, Lymphocyte Activation, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Mice, Intestinal mucosa, Cell Movement, intraepithelial lymphocytes, Intestine, Small, Immunology and Allergy, Interferon gamma, MESH: Animals, Intestinal Mucosa, Lung, MESH: Cell Movement, Interleukin-15, Mice, Inbred BALB C, Membrane Glycoproteins, MESH: Receptors, Antigen, T-Cell, alpha-beta, hemic and immune systems, General Medicine, MESH: CD8 Antigens, medicine.anatomical_structure, Liver, MESH: Cell Survival, Interleukin 15, MESH: Intestinal Mucosa, medicine.drug, Cell Survival, MESH: Interferon-gamma, CD8 Antigens, T cell, Immunology, MESH: Mice, Inbred BALB C, chemical and pharmacologic phenomena, Biology, digestive system, Interferon-gamma, thymic leukemia ag, Antigen, MHC class I, medicine, Animals, MESH: Lung, MESH: Lymphocyte Activation, MESH: Mice, mouse small intestine, Molecular biology, In vitro, biology.protein, Intraepithelial lymphocyte, MESH: Liver
Abstract: International audience; Thymus leukemia antigen (TL) is an MHC class Ib molecule that is highly conserved in rats and mice with no obvious human homolog. TL is expressed in mouse small intestinal epithelial cells and is known to interact with CD8alphaalpha homodimers, which are expressed by intraepithelial lymphocytes (IELs), some other T cell subsets and some non-T cells such as a subset of dendritic cells. We show here that TL is abundantly expressed on the basolateral surface of mouse small intestinal epithelial cells and that expression is abrogated in beta2m-/- mice but unaffected in TCR-/- mice or CD8alpha chain-/- mice. We demonstrate that the interaction between TL and CD8alphaalpha is not necessary for IEL survival in vitro or in vivo and does not modulate IEL trafficking in vivo. TL co-stimulation of alpha-CD3 antibody-activated IELs resulted in modestly enhanced production of IFN-gamma in one subset of IELs. The lack of effect on IEL survival and trafficking and the modest effect on IFN-gamma production suggest that the functional consequences of TL interaction with CD8alphaalpha as well as the more general biological role of TL in mucosal immunity remains to be discovered.
Published: 2004

33. IL-15 availability conditions homeostasis of peripheral natural killer T cells

Author: Thomas Ranson, Véronique Laloux, Odile Richard, Agnès Lehuen, James P. Di Santo, Christian A. J. Vosshenrich, Erwan Corcuff, Cytokines et Développement Lymphoïde, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie, génétique et traitement des maladies métaboliques et du diabète (UMR_S 561), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by grants from the Institut Pasteur, the Institut National de la Santé et de la Recherche Médicale, the Association pour la Recherche sur le Cancer, the Ligue National Contre le Cancer, and the Fondation de la Recherche Médicale., Vosshenrich, Christian, and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MESH: Signal Transduction, Time Factors, MESH: Antigens, CD1, MESH: Spleen, Receptors, Antigen, T-Cell, alpha-beta, [SDV]Life Sciences [q-bio], MESH: Interleukin-15, MESH: Flow Cytometry, MESH: Lymph Nodes, Antigens, CD1, Interleukin 21, Mice, 0302 clinical medicine, Cytotoxic T cell, MESH: Animals, IL-2 receptor, MESH: Bromodeoxyuridine, Interleukin-15, 0303 health sciences, Multidisciplinary, MESH: Receptors, Antigen, T-Cell, alpha-beta, ZAP70, MESH: Receptors, Antigen, T-Cell, Biological Sciences, Natural killer T cell, Flow Cytometry, Adoptive Transfer, Cell biology, Killer Cells, Natural, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Liver, MESH: Cell Survival, Interleukin 12, MESH: Cell Division, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cell Division, Signal Transduction, MESH: Killer Cells, Natural, [SDV.IMM] Life Sciences [q-bio]/Immunology, Cell Survival, MESH: Mice, Transgenic, T cell, Receptors, Antigen, T-Cell, Mice, Transgenic, Thymus Gland, Biology, 03 medical and health sciences, MESH: Mice, Inbred C57BL, medicine, Animals, Antigen-presenting cell, MESH: Mice, 030304 developmental biology, Interleukin-7, MESH: Time Factors, MESH: Thymus Gland, MESH: Interleukin-7, Mice, Inbred C57BL, MESH: Adoptive Transfer, Bromodeoxyuridine, MESH: Antigens, CD1d, Lymph Nodes, Antigens, CD1d, Spleen, 030215 immunology, MESH: Liver
Abstract: Steady-state numbers of peripheral lymphocyte are tightly controlled. For conventional T cells, signals delivered through the interaction of the T cell receptor (TCR) with antigen-loaded MHC molecules are required for the peripheral survival of naive T cells and for their homeostatic expansion in lymphopenic hosts. Cytokines, including IL-7, are also essential for survival of peripheral naive T cells. CD1d-restricted, Vα14+natural killer (NK)-T cells are a specialized autoreactive T subset with immunoregulatory activity. The relative roles of TCR engagement and cytokine signaling in the peripheral homeostasis of Vα14+NK-T cells were investigated. After adoptive transfer, the survival and expansion of peripheral Vα14+NK-T cells was independent of CD1d expression in the host. In contrast, IL-15 (but not IL-7) was required for maintenance of peripheral CD1d-reactive Vα14+T cells. Comparison of Vα14+T cell transfers into NK-proficient vs. deficient hosts suggests that NK-T cells and NK cells compete for peripheral resources. Our results indicate that IL-15 maintains the homeostasis of peripheral Vα14+NK-T cells. In contrast, TCR “tickling” of NK-T cells, if it occurs under steady-state conditions, does not by itself provide a sufficient signal for their peripheral survival.
Published: 2003

34. Low frequency of CD94/NKG2A+ T lymphocytes in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis, but not in asymptomatic carriers

Author: Veronique M. Braud, Charles R. M. Bangham, Koichiro Usuku, Mitsuhiro Osame, Nobutaka Eiraku, Mineki Saito, Jonathan Weber, Peter Goon, Yuetsu Tanaka, Akiko Saito, Graham P. Taylor, Emmanuel Hanon, Department of Immunology, Imperial College London, Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Paraparesis, Tropical Spastic, Receptors, Antigen, T-Cell, alpha-beta, Epitopes, T-Lymphocyte, MESH: T-Lymphocyte Subsets, CD8-Positive T-Lymphocytes, Biochemistry, MESH: Histocompatibility Antigens Class I, MESH: Proviruses, Interleukin 21, 0302 clinical medicine, Japan, Proviruses, HLA Antigens, T-Lymphocyte Subsets, MESH: Gene Products, tax, Cytotoxic T cell, IL-2 receptor, Receptors, Immunologic, MESH: Antigens, CD, MESH: HLA Antigens, MESH: Japan, 0303 health sciences, Human T-lymphotropic virus 1, MESH: Receptors, Antigen, T-Cell, alpha-beta, Receptors, Antigen, T-Cell, gamma-delta, Hematology, Gene Products, tax, Natural killer T cell, MESH: Antigens, CD94, MESH: CD8-Positive T-Lymphocytes, MESH: Gene Rearrangement, T-Lymphocyte, Paraparesis, Tropical Spastic, 3. Good health, medicine.anatomical_structure, Carrier State, Genes, T-Cell Receptor beta, Interleukin 12, [SDV.IMM]Life Sciences [q-bio]/Immunology, Receptors, Natural Killer Cell, MESH: Carrier State, NK Cell Lectin-Like Receptor Subfamily C, NK Cell Lectin-Like Receptor Subfamily D, MESH: Lymphocyte Count, T cell, Immunology, MESH: Genes, T-Cell Receptor beta, MESH: Immunodominant Epitopes, Biology, Gene Rearrangement, T-Lymphocyte, Natural killer cell, MESH: Epitopes, T-Lymphocyte, 03 medical and health sciences, MESH: Receptors, Antigen, T-Cell, gamma-delta, Antigens, CD, MESH: HTLV-I Infections, medicine, Humans, Lectins, C-Type, Lymphocyte Count, Antigen-presenting cell, MESH: Receptors, Immunologic, 030304 developmental biology, MESH: Human T-lymphotropic virus 1, MESH: Humans, Immunodominant Epitopes, MESH: Clone Cells, Histocompatibility Antigens Class I, Cell Biology, HTLV-I Infections, MESH: DNA, Viral, Clone Cells, DNA, Viral, MESH: Lectins, C-Type, 030215 immunology
Abstract: Human natural killer (NK)-cell receptors are expressed by NK cells and some T cells, primarily TCR+CD8+ cytotoxic T lymphocytes (CTLs). Inhibitory NK cell receptors (iNKRs) can down-regulate antigen-mediated T-cell effector functions, including cytotoxic activity and cytokine release. In the present study we demonstrate that CD3+ T cells that bind tetramers of HLA-E and express its ligand, the NK-cell inhibitory receptor CD94/NKG2A, were significantly decreased in frequency in patients with human T-cell lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) but not in asymptomatic HTLV-1 carriers. These cells were either alphabeta or gammadelta T cells. T-cell receptor (TCR) Vbeta-specific reverse transcription-polymerase chain reaction and spectratyping analysis revealed that the TCR repertoire in directly isolated HLA-E tetramer-positive cells from peripheral blood mononuclear cells was skewed in both HTLV-1-infected and healthy individuals. However, oligoclonally or monoclonally expanded levels of TCR Vbetawere more frequently detected within HTLV-1-infected individuals than healthy controls. Importantly, HLA-E tetramer-positive or NKG2A+ T cells from HTLV-1 patients do not express Tax and display different TCR usage from the immunodominant Tax11-19-specific CD8+ T cells, suggesting that they do not encounter HTLV-1-infected cells. The expression of NK cell-associated receptors by clonally expanded CD8+ T cells during chronic viral infection suggests that these receptors play a role in regulating CD8+ T cell-mediated antiviral immune responses and that a decrease of this cell subset results in an increased risk of inflammatory diseases such as HAM/TSP.
Published: 2003

35. CD8+ T lymphocytes in double alpha beta TCR transgenic mice. II. Competitive fitness of dual alpha beta TCR CD8+ T lymphocytes in the peripheral pools

Author: LEGRAND, Nicolas, Freitas, Antonio A., Biologie des Populations Lymphocytaires, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Cell Differentiation, Male, MESH: Mice, Transgenic, Cell Survival, Receptors, Antigen, T-Cell, alpha-beta, H-Y Antigen, chemical and pharmacologic phenomena, MESH: Transgenes, Mice, Transgenic, MESH: T-Lymphocyte Subsets, CD8-Positive T-Lymphocytes, Lymphocyte Activation, MESH: H-2 Antigens, MESH: Mice, Knockout, MESH: H-Y Antigen, Mice, MESH: Mice, Inbred C57BL, T-Lymphocyte Subsets, Animals, Homeostasis, MESH: Animals, Transgenes, MESH: Lymphocyte Activation, Histocompatibility Antigen H-2D, MESH: Mice, Mice, Knockout, MESH: Receptors, Antigen, T-Cell, alpha-beta, H-2 Antigens, Cell Differentiation, MESH: CD8-Positive T-Lymphocytes, MESH: Male, Mice, Inbred C57BL, MESH: Cell Survival, MESH: Homeostasis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Female
Abstract: International audience; We studied Rag2-deficient mice bearing two rearranged alphabeta TCR transgenes, both restricted to the MHC H-2D(b) class I molecule. We have previously shown that, in these DTg mice, most peripheral CD8 T cells express one TCRbeta chain associated with two TCRalpha chains, as in one-third of the mature T cells from normal mice. We examined the functional behavior of the dual-receptor CD8 T cells developing either in the absence or in the presence of self-Ag. The dual-receptor CD8 T cells, which develop in absence of self-Ag, show efficient responses to immunization and remain sensitive to induction of peripheral tolerance. In contrast to single TCR T cells, the dual-TCR cells, when tolerized upon exposure to high levels of self-Ag, are not deleted and therefore may exert important regulatory functions. When developing in the presence of self-Ag, the dual-receptor-expressing CD8 T cells escape central deletion, but are not fully competent to respond to cognate stimuli. Overall, we found that the dual-TCR CD8 T cells show a poor competitive value and can be out-competed by single-TCR cells, both in the course of immune responses and in reconstitution experiments. The decreased fitness of the dual-receptor cells may contribute to diminishing the autoimmune hazard that they could represent.
Published: 2001

36. CD8+ T lymphocytes in double alpha beta TCR transgenic mice. I. TCR expression and thymus selection in the absence or in the presence of self-antigen

Author: Antonio A. Freitas, Nicolas Legrand, Other departments, Biologie des Populations Lymphocytaires, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]
Subjects: Male, Receptors, Antigen, T-Cell, alpha-beta, Lymphocyte, CD8-Positive T-Lymphocytes, Autoantigens, MESH: Mice, Knockout, MESH: Down-Regulation, Mice, 0302 clinical medicine, Immunology and Allergy, Cytotoxic T cell, MESH: Animals, Transgenes, Mice, Knockout, 0303 health sciences, MESH: Receptors, Antigen, T-Cell, alpha-beta, biology, Cell Differentiation, hemic and immune systems, MESH: CD8-Positive T-Lymphocytes, DNA-Binding Proteins, MESH: Clonal Deletion, medicine.anatomical_structure, MESH: Autoantigens, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Cell Differentiation, MESH: Mice, Transgenic, T cell, H-Y Antigen, Immunology, Clonal Deletion, Down-Regulation, Mice, Transgenic, MESH: Transgenes, chemical and pharmacologic phenomena, Thymus Gland, Major histocompatibility complex, Lymphocytic choriomeningitis, MESH: H-2 Antigens, MESH: H-Y Antigen, 03 medical and health sciences, Antigen, MESH: Mice, Inbred C57BL, medicine, Animals, RNA, Messenger, Histocompatibility Antigen H-2D, MESH: Mice, 030304 developmental biology, MESH: RNA, Messenger, T-cell receptor, H-2 Antigens, MESH: Thymus Gland, medicine.disease, Molecular biology, MESH: Male, Mice, Inbred C57BL, biology.protein, MESH: Female, CD8, MESH: DNA-Binding Proteins, 030215 immunology
Abstract: We derived Rag2-deficient mice bearing two rearranged αβ TCR transgenes, one specific for the HY male Ag and the second specific for the gp33-41 peptide of lymphocytic choriomeningitis virus, both restricted to the MHC H-2Db class I molecule. We found that, in female double transgenic (DTg) mice, most CD8 T cells express only the TCRβ chain from the aHY transgene. By comparing the mRNA species for both β-chains, we observed that in T cells from DTg mice the aHY TCRβ chain transcripts are abundant, whereas the anti-lymphocytic choriomeningitis virus TCRβ chain transcripts are rare. In contrast to TCRβ chain expression, most of the T cells from DTg mice express two TCRα chains. We examined the thymus selection of the dual-receptor CD8 T cells in the presence of self-Ag. We found that the presence of a second TCRα chain allows a significant number of CD8 T cells expressing a self-reactive receptor to escape central deletion and migrate to the peripheral pools of male mice. Differences in TCR and coreceptor expression between female and male MoaHY and DTg mice suggest that peripheral T cell survival requires an optimal level of signaling, which implies a process of “adaptation” of lymphocyte populations to the host environment.
Published: 2001

37. Major histocompatibility class I molecules present Urtica dioica agglutinin, a superantigen of vegetal origin, to T lymphocytes

Author: Rovira, P., Abastado, J.-P., Buckle, M., Peumans, W. J., Truffa-Bachi, P., Immunophysiologie Moléculaire, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Physicochimie des Macromolecules Biologiques, Laboratorium voor Fytopathologie en Plantenbescherming, and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Signal Transduction, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, chemical and pharmacologic phenomena, MESH: Histocompatibility Antigens Class I, Mice, MESH: Lectins, MESH: Mice, Inbred C57BL, MESH: Superantigens, Lectins, Animals, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, Antigen Presentation, MESH: Receptors, Antigen, T-Cell, alpha-beta, Superantigens, Histocompatibility Antigens Class I, Histocompatibility Antigens Class II, MESH: Plant Lectins, MESH: Solubility, Mice, Inbred C57BL, MESH: T-Lymphocytes, Solubility, MESH: Antigen Presentation, MESH: Histocompatibility Antigens Class II, MESH: Cell Division, Female, Plant Lectins, MESH: Female, Cell Division, Signal Transduction
Abstract: International audience; The Urtica dioica agglutinin (UDA) shares with the superantigens the property of activating T cell subsets bearing particular Vbeta segments of the TCR. However, UDA is a lectin capable of binding to many glycoproteins on cell membranes. The implication of MHC versus other glycoproteins in UDA presentation was presently studied. Using mutant mice lacking MHC class I (MHC-I), MHC class II (MHC-II) or both MHC antigens, we provided evidence that MHC-I and MHC-II molecules serve as UDA receptors. Presentation by either one of these molecules ensured similar T cell responses and co-stimulatory signals were mandatory for optimal T cell activation and proliferation both in MHC-I and MHC-II contexts. Remarkably, in the absence of MHC molecules, UDA could not be efficiently presented to T cells by other glycosylated proteins. Surface plasmon resonance studies were used to confirm the binding of UDA to MHC-I molecules using a fusion protein consisting of MHC-I domains and beta2-microglobulin. The results indicated that the interaction between UDA and MHC-I molecules implicated lectin-binding site(s) of UDA. Taken together, our data demonstrate that, in addition to MHC-II antigens, MHC-I molecules serve as an alternative ligand for UDA.
Published: 1999

38. Tissue-specific segregation of CD1d-dependent and CD1d-independent NK T cells

Author: Gerard Eberl, Lees R, St, Smiley, Taniguchi M, Mj, Grusby, Hr, Macdonald, Ludwig Institute for Cancer Research, Harvard School of Public Health, Centre de Recherche en Économie et Statistique (CREST), Ecole Nationale de la Statistique et de l'Analyse de l'Information [Bruz] (ENSAI)-École polytechnique (X)-École Nationale de la Statistique et de l'Administration Économique (ENSAE Paris)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Économie et Statistique ( CREST ), and Ecole Nationale de la Statistique et de l'Analyse de l'Information [Bruz] ( ENSAI ) -École polytechnique ( X ) -École Nationale de la Statistique et de l'Administration Économique ( ENSAE ParisTech )
Subjects: Antigens, Differentiation, T-Lymphocyte, MESH : Protein Biosynthesis, MESH: Antigens, CD1, Receptors, Antigen, T-Cell, alpha-beta, MESH : Antigens, MESH: Antigens, CD4, MESH: Antigens, Differentiation, B-Lymphocyte, MESH: T-Lymphocyte Subsets, MESH : Antigens, Ly, Lymphocyte Activation, MESH : Proteins, Antigens, CD1, Mice, MESH: Genes, T-Cell Receptor alpha, T-Lymphocyte Subsets, MESH : Lectins, C-Type, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Antigens, Ly, MESH : Female, MESH: Animals, MESH: Proteins, MESH : Biomarkers, MESH: Organ Specificity, Mice, Inbred BALB C, MESH: Receptors, Antigen, T-Cell, alpha-beta, MESH : Mice, Nude, hemic and immune systems, MESH: Antigens, Ly, MESH : NK Cell Lectin-Like Receptor Subfamily B, Killer Cells, Natural, MESH : Genes, T-Cell Receptor alpha, MESH : Antigens, Differentiation, T-Lymphocyte, MESH: NK Cell Lectin-Like Receptor Subfamily B, MESH : Histocompatibility Antigens Class II, MESH : Receptors, Antigen, T-Cell, alpha-beta, Organ Specificity, MESH: Protein Biosynthesis, Antigens, Surface, CD4 Antigens, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Antigens, Female, MESH : Killer Cells, Natural, MESH : Antigens, Surface, Genes, T-Cell Receptor alpha, NK Cell Lectin-Like Receptor Subfamily B, MESH: Killer Cells, Natural, MESH : Antigens, CD1d, MESH: Antigens, Surface, CD8 Antigens, MESH: Mice, Inbred BALB C, Mice, Nude, chemical and pharmacologic phenomena, MESH : Mice, Inbred C57BL, Thymus Gland, MESH : Organ Specificity, MESH: Mice, Inbred C57BL, MESH : Mice, MESH: Mice, Nude, Animals, MESH : Thymus Gland, Lectins, C-Type, Antigens, MESH: Lymphocyte Activation, MESH: Mice, MESH : Lymphocyte Activation, MESH : Mice, Inbred BALB C, MESH : Antigens, Differentiation, B-Lymphocyte, Histocompatibility Antigens Class II, Proteins, MESH: Thymus Gland, MESH : T-Lymphocyte Subsets, Antigens, Differentiation, B-Lymphocyte, Mice, Inbred C57BL, MESH: Antigens, Differentiation, T-Lymphocyte, MESH : Antigens, CD1, MESH: Antigens, CD1d, Protein Biosynthesis, MESH: Biomarkers, MESH: Histocompatibility Antigens Class II, MESH : Antigens, CD4, MESH : Animals, MESH: Antigens, CD8, Antigens, CD1d, MESH : Antigens, CD8, MESH: Female, MESH: Lectins, C-Type, Biomarkers
Abstract: International audience; NKT cells, defined as T cells expressing the NK cell marker NK1.1, are involved in tumor rejection and regulation of autoimmunity via the production of cytokines. We show in this study that two types of NKT cells can be defined on the basis of their reactivity to the monomorphic MHC class I-like molecule CD1d. One type of NKT cell is positively selected by CD1d and expresses a biased TCR repertoire together with a phenotype found on activated T cells. A second type of NKT cell, in contrast, develops in the absence of CD1d, and expresses a diverse TCR repertoire and a phenotype found on naive T cells and NK cells. Importantly, the two types of NKT cells segregate in distinct tissues. Whereas thymus and liver contain primarily CD1d-dependent NKT cells, spleen and bone marrow are enriched in CD1d-independent NKT cells. Collectively, our data suggest that recognition of tissue-specific ligands by the TCR controls localization and activation of NKT cells.
Published: 1999

39. Peptide antigen or superantigen-induced down-regulation of TCRs involves both stimulated and unstimulated receptors

Author: Florence Niedergang, Dautry-Varsat, A., Alcover, A., Biologie des Interactions Cellulaires (BIC), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: Superantigens, MESH: CD3 Complex, MESH: Humans, MESH: Receptors, Antigen, T-Cell, alpha-beta, CD3 Complex, MESH: Phosphorylation, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, MESH: Transfection, Immunology, Down-Regulation, hemic and immune systems, chemical and pharmacologic phenomena, Transfection, biological factors, MESH: Down-Regulation, Jurkat Cells, MESH: T-Lymphocytes, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, MESH: Superantigens, MESH: Jurkat Cells, Immunology and Allergy, Humans, Phosphorylation
Abstract: T cell activation by peptide/MHC complexes, superantigens, or mAbs induces the down-regulation of cell surface TCRs. We addressed the question of whether TCR down-modulation affects only TCRs that had directly interacted with their ligand or whether down-modulation could also affect TCRs that had not interacted with their ligand. To this end, we generated T cells coexpressing equal levels of two different TCRs by transfecting the appropriate cDNAs into cells of the human T cell line, Jurkat. Each set of TCRs can be distinguished by means of anti-Vbeta mAbs and can be stimulated separately with peptide Ag, bacterial superantigens, or mAbs. We found that activation of these cells with each of these stimuli down-modulated not only directly stimulated TCR complexes but also unstimulated ones. Comodulation of stimulated and unstimulated receptors may reflect functional interactions between surface TCRs that could take place during Ag or superantigen recognition by T cells without the need for ligand cross-linking. Consistent with this idea, both stimulated and unstimulated receptors colocalized in patches on the cell surface after activation.
Published: 1997

40. Differential requirements for survival and proliferation of CD8 naïve or memory T cells

Author: Corinne Tanchot, François A. Lemonnier, Benedita Rocha, Béatrice Pérarnau, Antonio A. Freitas, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunité Cellulaire Antivirale, Institut Pasteur [Paris], Dynamiques Lymphocytaires, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Necker Enfants-Malades (INEM) ( INEM - UM 111 (UMR 8253 / U1151) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Receptors, Antigen, T-Cell, alpha-beta, MESH: T-Lymphocyte Subsets, CD8-Positive T-Lymphocytes, Lymphocyte Activation, Mice, 0302 clinical medicine, T-Lymphocyte Subsets, Cytotoxic T cell, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, MESH: Animals, IL-2 receptor, 0303 health sciences, MESH : Cell Survival, Multidisciplinary, MESH: Receptors, Antigen, T-Cell, alpha-beta, MESH : Adoptive Transfer, CD28, MESH : Cell Division, MESH : CD8-Positive T-Lymphocytes, Adoptive Transfer, MESH: CD8-Positive T-Lymphocytes, MESH : Mice, Transgenic, MESH : Receptors, Antigen, T-Cell, alpha-beta, MESH: Cell Survival, MESH: Immunologic Memory, MESH: Cell Division, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Cell Division, MESH : Immunologic Memory, Cell Survival, MESH: Mice, Transgenic, MESH : Male, H-Y Antigen, Mice, Transgenic, MESH : Mice, Inbred C57BL, Biology, Major histocompatibility complex, MESH: H-2 Antigens, MESH: H-Y Antigen, 03 medical and health sciences, MESH: Mice, Inbred C57BL, MHC class I, MESH : Mice, Animals, Antigen-presenting cell, Histocompatibility Antigen H-2D, MESH: Lymphocyte Activation, MESH: Mice, MESH : H-Y Antigen, MESH : Lymphocyte Activation, 030304 developmental biology, MESH : H-2 Antigens, H-2 Antigens, MHC restriction, MESH : T-Lymphocyte Subsets, MESH: Male, Mice, Inbred C57BL, MESH: Adoptive Transfer, Immunology, biology.protein, MESH : Animals, Immunologic Memory, MESH: Female, CD8, 030215 immunology
Abstract: The requisite molecular interactions for CD8 T cell memory were determined by comparison of monoclonal naı̈ve and memory CD8+T cells bearing the T cell receptor (TCR) for the HY antigen. Naı̈ve T cells required only the right major histocompatibility complex (MHC) class I–restricting molecule to survive; to expand, they also needed antigen. In contrast, for survival, memory cells did not require the restricting MHC allele, but needed only a nonspecific class I; for expansion the correct class I, but not antigen, was required. Thus, maintenance of CD8 T cell memory still required TCR–MHC class I interactions, but memory T cells may have a lower functional activation threshold that facilitates secondary responses.
Published: 1997

41. Persistence of V beta 6+ T cells in Mls-1a mice. A role for the third complementarity-determining region (CDR3) of the T cell receptor beta chain in superantigen recognition

Author: Ja, Chies, Gilles Marodon, Am, Joret, Regnault A, Mp, Lembezat, Rocha B, Aa, Freitas, Dynamiques Lymphocytaires, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie Moléculaire du Gène, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut Necker Enfants-Malades (INEM) ( INEM - UM 111 (UMR 8253 / U1151) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: Male, MESH : Molecular Sequence Data, MESH : Gene Rearrangement, beta-Chain T-Cell Antigen Receptor, MESH : Male, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, Molecular Sequence Data, Immunoglobulin Variable Region, MESH: Mice, Inbred BALB C, MESH: Immunoglobulin Variable Region, chemical and pharmacologic phenomena, MESH: Base Sequence, Lymphocyte Activation, Mice, MESH: Superantigens, MESH : Mice, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Animals, MESH : Female, MESH: Animals, MESH : Superantigens, Gene Rearrangement, beta-Chain T-Cell Antigen Receptor, MESH : Immunoglobulin Variable Region, MESH: Lymphocyte Activation, MESH: Mice, MESH : Lymphocyte Activation, MESH : Mice, Inbred BALB C, MESH : T-Lymphocytes, Antigen Presentation, Mice, Inbred BALB C, Superantigens, MESH: Molecular Sequence Data, MESH: Receptors, Antigen, T-Cell, alpha-beta, Base Sequence, hemic and immune systems, MESH: Male, MESH: T-Lymphocytes, MESH : Receptors, Antigen, T-Cell, alpha-beta, MESH: Antigen Presentation, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Base Sequence, Female, MESH : Animals, MESH : Antigen Presentation, MESH: Female, MESH: Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
Abstract: International audience; We have studied V alpha 2 and J beta usage by V beta 6+CD4+ peripheral T cells isolated from the congenic mice strains BALB/c (Mls-1b) and BALB.D2 (Mls-1a). We found that the TCR beta-chain of V beta 6+CD4+ T cells present in adult Mls-1a mice differed from those in Mls-1b mice; the fraction of V beta 6+CD4+T cells using the J beta 2.7 segment was reduced, while the number of V beta 6+CD4+ T cells using J beta 1.2 was augmented. These results indicate that the CDR3 region of the TCR beta-chain participates in recognition of the Mls superantigen. We also found that in Mls-1a mice an increased fraction of V beta 6+CD4+ T cells expressed the V alpha 2 chain. The study of J beta usage by V beta 6+CD4+V alpha 2+ and V beta 6+CD4+V alpha 2- T cells indicates that both J beta segment and TCR V alpha 2 chain expression confer complementary protection against deletion by Mls-1a superantigen. These results suggest a novel view of Mls-1a-driven selection, where the CDR3 region of the V beta chain modulates superantigen recognition, and the affinity/avidity of the TCR-MHC-superantigen complex determine the fate of the T cell.
Published: 1995

42. The Staphylococcus aureus enterotoxin B superantigen induces specific T cell receptor down-regulation by increasing its internalization

Author: Alice Dautry-Varsat, Michael John Owen, Colin R.A. Hewitt, Florence Niedergang, Agnès Hémar, Andrés Alcover, Biologie des Interactions Cellulaires (BIC), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Imperial Cancer Research Fund, and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: CD3 Complex, CD3 Complex, Receptor expression, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, Fluorescent Antibody Technique, Hemagglutinin Glycoproteins, Influenza Virus, Biochemistry, MESH: Down-Regulation, MESH: Dose-Response Relationship, Drug, Enterotoxins, 0302 clinical medicine, MESH: Superantigens, Superantigen, MESH: Staphylococcus aureus, MESH: Enterotoxins, Tumor Cells, Cultured, Cytotoxic T cell, MESH: Microscopy, Confocal, MESH: Fluorescent Antibody Technique, 0303 health sciences, Lymphokines, MESH: Receptors, Antigen, T-Cell, alpha-beta, Microscopy, Confocal, Superantigens, MESH: Hemagglutinin Glycoproteins, Influenza Virus, hemic and immune systems, Endocytosis, Endocytic vesicle, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, MESH: Endocytosis, Protein Binding, Staphylococcus aureus, Down-Regulation, Hemagglutinins, Viral, chemical and pharmacologic phenomena, Biology, Microbiology, 03 medical and health sciences, Cell surface receptor, MESH: Protein Binding, Humans, MESH: Tumor Cells, Cultured, Antigen-presenting cell, Molecular Biology, 030304 developmental biology, Organelles, MESH: Lymphokines, MESH: Humans, Dose-Response Relationship, Drug, T-cell receptor, Histocompatibility Antigens Class II, Cell Biology, T lymphocyte, Molecular biology, MESH: T-Lymphocytes, MESH: Histocompatibility Antigens Class II, 030215 immunology, MESH: Organelles, MESH: Hemagglutinins, Viral
Abstract: Superantigens are able to stimulate T lymphocyte populations expressing T cell antigen receptors (TCR) belonging to particular V beta families. Moreover, the presence of these superantigens may induce long term unresponsiveness (anergy) of these sensitive cells. Some bacterial toxins are potent superantigens. We have analyzed in vitro the capacity of some Staphylococcus aureus enterotoxin superantigens to modulate T cell antigen receptor expression and the cellular mechanisms involved. Staphylococcus enterotoxin B (SEB) induced rapid down-regulation of surface T cell antigen receptors in V beta 3-expressing T lymphocytes, as assessed by flow cytometry. This phenomenon was a consequence of the direct interaction between the toxin and the TCR since it was observed in the absence of cells expressing major histocompatibility complex class II molecules. The cellular mechanism involved in SEB-induced down-regulation of TCR was further investigated. Immunofluorescence and confocal microscopy experiments showed that toxin B induced intracellular accumulation of TCR.CD3 in endocytic vesicles. Moreover, SEB induced an increase in T cell receptor endocytosis as measured using radiolabeled Fab fragments of an anti-CD3 monoclonal antibody. Taken together, our observations indicate that Staphylococcus enterotoxin B superantigen induced changes in the dynamics of surface T cell receptors, which resulted in the fast reduction of membrane receptor numbers.
Published: 1995

43. Anergy and exhaustion are independent mechanisms of peripheral T cell tolerance

Author: Benedita Rocha, Alf Grandien, Antonio A. Freitas, Institut Necker Enfants-Malades (INEM) ( INEM - UM 111 (UMR 8253 / U1151) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Immunobiologie, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Vougny, Marie-Christine
Subjects: Male, MESH : Molecular Sequence Data, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, MESH : Antigens, MESH : Lymphocyte Transfusion, MESH: Base Sequence, Mice, 0302 clinical medicine, Immunology and Allergy, Cytotoxic T cell, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, MESH : Female, IL-2 receptor, MESH: Bone Marrow Transplantation, MESH: Chimera, Bone Marrow Transplantation, 0303 health sciences, MESH: Receptors, Antigen, T-Cell, alpha-beta, biology, MESH : Immune Tolerance, Articles, MESH : Mice, Transgenic, 3. Good health, medicine.anatomical_structure, MESH : Receptors, Antigen, T-Cell, alpha-beta, Lymphocyte Transfusion, MESH: Lymphocyte Transfusion, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Antigens, MESH: Immune Tolerance, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Mice, Transgenic, T cell, MESH : Sex Factors, MESH : Male, Immunology, Naive B cell, Molecular Sequence Data, Mice, Transgenic, MESH : Mice, Inbred C57BL, 03 medical and health sciences, Sex Factors, Antigen, MESH: Sex Factors, MESH: Mice, Inbred C57BL, MESH : Mice, medicine, Immune Tolerance, Animals, Antigens, Antigen-presenting cell, MESH: Mice, B cell, 030304 developmental biology, MESH : T-Lymphocytes, CD40, MESH: Molecular Sequence Data, Base Sequence, Chimera, MESH : Bone Marrow Transplantation, Molecular biology, MESH: Male, Mice, Inbred C57BL, MESH: T-Lymphocytes, biology.protein, MESH : Chimera, MESH : Base Sequence, MESH : Animals, MESH: Female, 030215 immunology
Abstract: International audience; We studied the interactions of male-specific T cell receptor (TCR)-alpha/beta-transgenic (TG) cells with different concentrations of male antigen in vivo. We constructed mouse chimeras expressing different amounts of male antigen by injecting thymectomized, lethally irradiated mice with various ratios of male (immunoglobulin [Ig] Ha) and female (IgHb) bone marrow. These chimeras were injected with male-specific TCR-alpha/beta-trangenic cells. These experiments allowed us to monitor antigen persistence and characterize antigen-specific T cells in terms of their frequency, reactivity, and effector functions (as tested by elimination of male B cells in vivo). In the absence of antigen, virgin TG cells persisted but did not expand. Transient exposure to antigen resulted in cell expansion, followed by the persistence of increased numbers of antigen-reactive T cells. In contrast, antigen persistence was followed by two independent mechanisms of tolerance induction: anergy (at high antigen concentrations), where T cells did not differentiate into effector functions but persisted in vivo as unresponsive T cells, and exhaustion (at lower antigen concentrations), where differentiation into effector functions (B cell elimination) occurred but was followed by the disappearance of antigen-specific T cells.
Published: 1995

44. Skin-Resident Murine Dendritic Cell Subsets Promote Distinct and Opposing Antigen-Specific T Helper Cell Responses

Author: Aleh Bobr, Botond Z. Igyártó, Bernard Malissen, Judith Berman, Maryam Gerami-Nejad, Daniela Ortner, Sandra Zurawski, Gerard Zurawski, Brian T. Edelson, Krystal M. Haley, Daniel H. Kaplan, Center for Immunology - University of Minnesota, University of Minnesota [Twin Cities] (UMN), University of Minnesota System-University of Minnesota System, Department of Molecular & Cellular Biology - University of Minnesota, Washington University School of Medecine - Department of Pathology & Immunology, Washington University School of Medecine [Saint Louis, MO], Baylor Institute for Immunology Research (BIIR), Baylor College of Medecine, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Washington University School of Medicine [Saint Louis, MO], and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adoptive cell transfer, Receptors, Antigen, T-Cell, alpha-beta, MESH: Th17 Cells, MESH: T-Lymphocyte Subsets, Lymphocyte Activation, MESH: Mice, Knockout, Mice, 0302 clinical medicine, T-Lymphocyte Subsets, Candida albicans, Immunology and Allergy, Cytotoxic T cell, MESH: Animals, Cells, Cultured, Skin, Mice, Knockout, 0303 health sciences, MESH: Receptors, Antigen, T-Cell, alpha-beta, biology, MESH: Dendritic Cells, integumentary system, Candidiasis, hemic and immune systems, T helper cell, Adoptive Transfer, MESH: Candidiasis, 3. Good health, Cell biology, Infectious Diseases, medicine.anatomical_structure, Basic-Leucine Zipper Transcription Factors, MESH: Repressor Proteins, Antigens, Surface, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Cells, Cultured, Langerin, MESH: Cross-Priming, MESH: Mice, Transgenic, MESH: Antigens, Surface, T cell, Immunology, Mice, Transgenic, chemical and pharmacologic phenomena, MESH: Basic-Leucine Zipper Transcription Factors, Article, 03 medical and health sciences, Immune system, Cross-Priming, Antigen, MESH: Skin, MESH: Mice, Inbred C57BL, MESH: Mannose-Binding Lectins, medicine, Animals, Lectins, C-Type, MESH: Lymphocyte Activation, MESH: Mice, 030304 developmental biology, Antigens, Bacterial, MESH: Candida albicans, Dendritic cell, Dendritic Cells, Mice, Inbred C57BL, Repressor Proteins, Disease Models, Animal, MESH: Adoptive Transfer, Mannose-Binding Lectins, biology.protein, Th17 Cells, MESH: Disease Models, Animal, MESH: Lectins, C-Type, MESH: Antigens, Bacterial, 030215 immunology
Abstract: International audience; Skin-resident dendritic cells (DCs) are well positioned to encounter cutaneous pathogens and are required for the initiation of adaptive immune responses. There are at least three subsets of skin DC- Langerhans cells (LC), Langerin(+) dermal DCs (dDCs), and classic dDCs. Whether these subsets have distinct or redundant function in vivo is poorly understood. Using a Candida albicans skin infection model, we have shown that direct presentation of antigen by LC is necessary and sufficient for the generation of antigen-specific T helper-17 (Th17) cells but not for the generation of cytotoxic lymphocytes (CTLs). In contrast, Langerin(+) dDCs are required for the generation of antigen specific CTL and Th1 cells. Langerin(+) dDCs also inhibited the ability of LCs and classic DCs to promote Th17 cell responses. This work demonstrates that skin-resident DC subsets promote distinct and opposing antigen-specific responses.
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45. Cooperative activation of TCRs by enterotoxin superantigens

Author: Florence Niedergang, Dautry-Varsat, A., Alcover, A., Biologie des Interactions Cellulaires (BIC), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Enzyme Activation, Staphylococcus aureus, Receptors, Antigen, T-Cell, alpha-beta, Immunology, Receptors, Antigen, T-Cell, chemical and pharmacologic phenomena, MESH: T-Lymphocyte Subsets, Lymphocyte Activation, MESH: Protein-Tyrosine Kinases, MESH: Tyrosine, Cell Line, Enterotoxins, Jurkat Cells, MESH: Superantigens, T-Lymphocyte Subsets, MESH: Enterotoxins, MESH: Jurkat Cells, MESH: Staphylococcus aureus, Humans, Immunology and Allergy, MESH: Lymphocyte Activation, MESH: Receptor-CD3 Complex, Antigen, T-Cell, MESH: Receptors, Antigen, T-Cell, alpha-beta, MESH: Humans, Superantigens, ZAP-70 Protein-Tyrosine Kinase, Membrane Proteins, hemic and immune systems, MESH: Receptors, Antigen, T-Cell, MESH: ZAP-70 Protein-Tyrosine Kinase, Protein-Tyrosine Kinases, MESH: Cell Line, Enzyme Activation, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Receptor-CD3 Complex, Antigen, T-Cell, Tyrosine, MESH: Membrane Proteins
Abstract: Disponible gratuitement sur le site de l'éditeur. http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=9834088; International audience; Staphylococcus enterotoxin superantigens are potent T cell activators. To gain new insights into the mechanism of T cell activation induced by these superantigens, we investigated the recruitment of signaling molecules in this process. Here, we show that enterotoxin superantigen activation can be transmitted to TCR-CD3 complexes that did not interact with their ligand. Indeed, by studying cells expressing two distinct TCRs, we found that enterotoxin superantigens induced tyrosine phosphorylation of TCRzeta subunits, the recruitment and tyrosine phosphorylation of the protein tyrosine kinase ZAP-70, and an increase in protein tyrosine kinase activity of both directly stimulated and unstimulated TCR-CD3 complexes. As the involvement of unstimulated TCR-CD3 complexes in signal transduction would increase the number of signaling molecules and, therefore, the efficiency of T cell activation, these data provide a novel explanation for the ability of enterotoxin superantigens to potently activate T lymphocytes.

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