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1. Invariant NKT cells regulate the CD8 T cell response during Theiler's virus infection

Author

Roland S. Liblau, Maria Leite-de-Moraes, Magali Mas, Lucie Beaudoin, Jean-François Bureau, Lennart T. Mars, Agnès Lehuen, Jan Bauer, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department Neuroimmunology, Medizinische Universität Wien = Medical University of Vienna-Center for Brain Research, 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), Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM), the Centre National de la Recherche Scientifique (CNRS), the French MS society (ARSEP), the Midi-Pyrénées Region, and the Agence National de la Recherche (ANR-06-MIME), Medizinische Universität Wien = Medical University of Vienna-Center for Brain Research [Vienna, Austria], Medizinische Universität Wien = Medical University of Vienna, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Bos, Mireille, Centre de Physiopathologie de Toulouse Purpan ( CPTP ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Medical University of Vienna-Center for Brain Research, Cytokines, hématopoïèse et réponse immune ( CHRI ), Génétique fonctionnelle des Maladies infectieuses, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Central Nervous System, MESH: Inflammation, Mouse, MESH: Spleen, Encephalomyelitis, viruses, Neuroimmunology, Priming (immunology), MESH : Poliomyelitis, MESH: Lymph Nodes, MESH: T-Lymphocyte Subsets, Immune Privilege, CD8-Positive T-Lymphocytes, Lymphocyte Activation, Epitope, Epitopes, Mice, T-Lymphocyte Subsets, Cytotoxic T cell, MESH: Animals, Immune Response, MESH : Lymph Nodes, Multidisciplinary, T Cells, MESH : Central Nervous System, virus diseases, Animal Models, MESH : CD8-Positive T-Lymphocytes, Natural killer T cell, MESH: CD8-Positive T-Lymphocytes, MESH : Mice, Transgenic, Innate Immunity, 3. Good health, medicine.anatomical_structure, MESH: Encephalomyelitis, Medicine, Research Article, MESH : Spleen, MESH: Epitopes, MESH: Mice, Transgenic, Immune Cells, T cell, Science, Immunology, Mice, Transgenic, MESH : Mice, Inbred C57BL, MESH : Epitopes, Biology, Model Organisms, Immune system, Theilovirus, MESH: Mice, Inbred C57BL, MESH : Mice, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, MESH: Central Nervous System, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Lymphocyte Activation, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Immunity to Infections, MESH: Mice, MESH : Lymphocyte Activation, MESH : Encephalomyelitis, Inflammation, MESH : Inflammation, T-cell receptor, Immunity, Immunoregulation, MESH : Theilovirus, Immunologic Subspecialties, medicine.disease, MESH : Natural Killer T-Cells, Virology, MESH : T-Lymphocyte Subsets, Mice, Inbred C57BL, MESH: Theilovirus, MESH: Natural Killer T-Cells, MESH: Poliomyelitis, Natural Killer T-Cells, Clinical Immunology, MESH : Animals, Lymph Nodes, Spleen, Poliomyelitis
Abstract

International audience; Invariant NKT cells are innate lymphocytes with a broad tissue distribution. Here we demonstrate that iNKT cells reside in the central nervous system (CNS) in the absence of inflammation. Their presence in the CNS dramatically augments following inoculation of C57Bl/6 mice with the neurotropic Theiler's murine encephalomyelitis virus (TMEV). At the peak of inflammation the cellular infiltrate comprises 45,000 iNKT cells for 1250 CD8 T cells specific for the immunodominant TMEV epitope. To study the interaction between these two T cell subsets, we infected both iNKT cell deficient Jα18(-/-) mice and iNKT cell enriched Vα14 transgenic mice with TMEV. The CD8 T cell response readily cleared TMEV infection in the iNKT cell deficient mice. However, in the iNKT cell enriched mice TMEV infection persisted and was associated with significant mortality. This was caused by the inhibition of the CD8 T cell response in the cervical lymph nodes and spleen after T cell priming. Taken together we demonstrate that iNKT cells reside in the CNS in the absence of inflammation and that their enrichment is associated with the inhibition of the anti-viral CD8 T cell response and an augmented mortality during acute encephalomyelitis.

Published
2014
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2. Characterization of resident and migratory dendritic cells in human lymph nodes

Author

Xavier Sastre-Garau, Elodie Segura, Marie-Hélène Donnadieu, Sebastian Amigorena, Jenny Valladeau-Guilemond, Vassili Soumelis, Immunité et cancer (U932), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie-Université Paris Descartes - Paris 5 (UPD5), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Biologie des Tumeurs, Institut Curie, Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), INSTITUT CURIE, Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Curie [Paris], Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
MESH: Antigens, CD1, Lipopolysaccharide Receptors, MESH : Receptors, Cell Surface, MESH: Lymph Nodes, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Antigens, CD1, 0302 clinical medicine, Cell Movement, MESH : Lectins, C-Type, Immunology and Allergy, MESH : Cell Movement, MESH: Cell Movement, MESH : Lymph Nodes, MESH : Mannose-Binding Lectins, Skin, MESH: Receptors, Cell Surface, 0303 health sciences, integumentary system, MESH: Dendritic Cells, MESH: Antigens, CD14, Cell Polarity, hemic and immune systems, 3. Good health, medicine.anatomical_structure, Lymph, MESH: Cell Polarity, MESH : Cell Polarity, Mannose Receptor, T cell, Immunology, Spleen, Receptors, Cell Surface, chemical and pharmacologic phenomena, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, 03 medical and health sciences, Immune system, Th2 Cells, Antigen, MESH: Skin, MESH: Th2 Cells, MESH: Mannose-Binding Lectins, medicine, MESH : Skin, Humans, Lectins, C-Type, 030304 developmental biology, MESH: Humans, MESH : Humans, Brief Definitive Report, Dendritic Cells, In vitro, MESH : Th2 Cells, MESH : Antigens, CD14, Mannose-Binding Lectins, MESH : Antigens, CD1, Tonsil, MESH : Dendritic Cells, Lymph Nodes, CD8, MESH: Lectins, C-Type, 030215 immunology
Abstract

Human skin-draining lymph nodes contain functionally distinct subsets of resident and migratory dendritic cells., Dendritic cells (DCs) initiate adaptive immune responses in lymph nodes (LNs). In mice, LN DCs can be divided into resident and tissue-derived populations, the latter of which migrate from the peripheral tissues. In humans, different subsets of DCs have been identified in the blood, spleen, and skin, but less is known about populations of resident and migratory tissue-derived DCs in LNs. We have analyzed DCs in human LNs and identified two populations of resident DCs that are present in all LNs analyzed, as well as in the spleen and tonsil, and correspond to the two known blood DC subtypes. We also identify three main populations of skin-derived migratory DCs that are present only in skin-draining LNs and correspond to the DC subsets found in the skin. Resident DCs subsets induce both Th1 and Th2 cytokines in naive allogeneic T lymphocytes, whereas the corresponding blood subsets failed to induce efficient Th2 polarization. LN-resident DCs also cross-present antigen without in vitro activation, whereas blood DCs fail to do so. Among migratory DCs, one subset was poor at both CD4+ and CD8+ T cell activation, whereas the other subsets induced only Th2 polarization. We conclude that in humans, skin-draining LNs host both resident and migratory DC subsets with distinct functional abilities.

Published
2012
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3. RANKL induces organized lymph node growth by stromal cell proliferation

Author

S. Lori Bridal, Marion Decossas, Sylvestre Chea, Vincent Duheron, Yongwon Choi, Mattéo R. Bosisio, Frédéric Lézot, Rachel Golub, Christopher G. Mueller, Ariane Berdal, Estelle Hess, Hideo Yagita, Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie des Adaptations Nutritionnelles (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Lymphopoïèse, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Imagerie Paramétrique (LIP), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Centre National de la Recherche Scientifique (CNRS), ECHOSENS S.A., Echosens, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Department of Immunology, Juntendo University School of Medicine, Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Pennsylvania [Philadelphia], Immunologie et chimie thérapeutiques ( ICT ), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -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 Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire d'Imagerie Paramétrique ( LIP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR58-Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
MESH: Chemokine CCL19, MESH: Lymph Nodes, MESH : Hair Follicle, Mice, 0302 clinical medicine, MESH : Cell Proliferation, Homeostasis, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, MESH: Animals, Lymph node, MESH : Lymph Nodes, 0303 health sciences, MESH: RANK Ligand, MESH : Mice, Transgenic, MESH : Chemokine CXCL13, Cell biology, medicine.anatomical_structure, Lymphatic system, RANKL, MESH: Homeostasis, MESH : Homeostasis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Hair Follicle, MESH : RANK Ligand, MESH: Chemokine CXCL13, Hair Follicle, Stromal cell, MESH: Mice, Transgenic, Immunology, Mice, Transgenic, Biology, 03 medical and health sciences, MESH: Cell Proliferation, MESH : Mice, medicine, Lymph node stromal cell, Animals, CXCL13, MESH: Mice, B cell, Cell Proliferation, 030304 developmental biology, MESH: Immune System, RANK Ligand, Hair follicle, Chemokine CXCL13, MESH : Chemokine CCL19, Immune System, MESH : Stromal Cells, MESH : Immune System, biology.protein, Chemokine CCL19, Lymph Nodes, MESH : Animals, Stromal Cells, MESH: Stromal Cells, 030215 immunology
Abstract

RANK and its ligand RANKL play important roles in the development and regulation of the immune system. We show that mice transgenic for Rank in hair follicles display massive postnatal growth of skin-draining lymph nodes. The proportions of hematopoietic and nonhematopoietic stromal cells and their organization are maintained, with the exception of an increase in B cell follicles. The hematopoietic cells are not activated and respond to immunization by foreign Ag and adjuvant. We demonstrate that soluble RANKL is overproduced from the transgenic hair follicles and that its neutralization normalizes lymph node size, inclusive area, and numbers of B cell follicles. Reticular fibroblastic and vascular stromal cells, important for secondary lymphoid organ formation and organization, express RANK and undergo hyperproliferation, which is abrogated by RANKL neutralization. In addition, they express higher levels of CXCL13 and CCL19 chemokines, as well as MAdCAM-1 and VCAM-1 cell-adhesion molecules. These findings highlight the importance of tissue-derived cues for secondary lymphoid organ homeostasis and identify RANKL as a key molecule for controlling the plasticity of the immune system.

Published
2012
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4. Rapid Dissemination of SIV Follows Multisite Entry after Rectal Inoculation

Author

Rémi Cheynier, Jean-Luc Prétet, Valérie Messent, Anna Bogdanova, Magali Rancez, Cécile Butor, Alice Michel-Salzat, Evelyne Souil, Anne Couëdel-Courteille, Patricia Ribeiro dos Santos, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Université Paris Diderot - Paris 7 ( UPD7 ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), and Université Paris Diderot - Paris 7 (UPD7)

Subjects
Male, viruses, Simian Acquired Immunodeficiency Syndrome, lcsh:Medicine, MESH: Lymph Nodes, Macaque, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, MESH: Rectum, Immunodeficiency Viruses, MESH: Animals, MESH : Mucous Membrane, 030212 general & internal medicine, lcsh:Science, MESH : Lymph Nodes, 0303 health sciences, Multidisciplinary, biology, MESH : Simian Acquired Immunodeficiency Syndrome, Animal Models, Viral Load, 3. Good health, Host-Pathogen Interaction, AIDS, medicine.anatomical_structure, MESH : Rectum, Medicine, Infectious diseases, Simian Immunodeficiency Virus, Lymph, MESH: Simian Acquired Immunodeficiency Syndrome, MESH : Macaca mulatta, Research Article, MESH: Simian immunodeficiency virus, Viral Entry, MESH : Male, HIV prevention, Sexually Transmitted Diseases, Retrovirology and HIV immunopathogenesis, Rectum, [SDV.CAN]Life Sciences [q-bio]/Cancer, Viral diseases, Microbiology, Virus, MESH: Macaca mulatta, 03 medical and health sciences, Model Organisms, Antigen, Immunity, biology.animal, Virology, medicine, Animals, Biology, 030304 developmental biology, Lamina propria, Mucous Membrane, lcsh:R, Host Cells, MESH: Mucous Membrane, HIV, Macaca mulatta, MESH: Male, Animal Models of Infection, MESH : Simian immunodeficiency virus, Viral replication, Immunology, lcsh:Q, MESH : Animals, Lymph Nodes, Viral Transmission and Infection
Abstract

International audience; Receptive ano-rectal intercourse is a major cause of HIV infection in men having sex with men and in heterosexuals. Current knowledge of the mechanisms of entry and dissemination during HIV rectal transmission is scarce and does not allow the development of preventive strategies. We investigated the early steps of rectal infection in rhesus macaques inoculated with the pathogenic isolate SIVmac251 and necropsied four hours to nine days later. All macaques were positive for SIV. Control macaques inoculated with heat-inactivated virus were consistently negative for SIV. SIV DNA was detected in the rectum as early as four hours post infection by nested PCR for gag in many laser-microdissected samples of lymphoid aggregates and lamina propria but never in follicle-associated epithelium. Scarce SIV antigen positive cells were observed by immunohistofluorescence in the rectum, among intraepithelial and lamina propria cells as well as in clusters in lymphoid aggregates, four hours post infection and onwards. These cells were T cells and non-T cells that were not epithelial cells, CD68(+) macrophages, DC-SIGN(+) cells or fascin(+) dendritic cells. DC-SIGN(+) cells carried infectious virus. Detection of Env singly spliced mRNA in the mucosa by nested RT-PCR indicated ongoing viral replication. Strikingly, four hours post infection colic lymph nodes were also infected in all macaques as either SIV DNA or infectious virus was recovered. Rapid SIV entry and dissemination is consistent with trans-epithelial transport. Virions appear to cross the follicle-associated epithelium, and also the digestive epithelium. Viral replication could however be more efficient in lymphoid aggregates. The initial sequence of events differs from both vaginal and oral infections, which implies that prevention strategies for rectal transmission will have to be specific. Microbicides will need to protect both digestive and follicle-associated epithelia. Vaccines will need to induce immunity in lymph nodes as well as in the rectum.

Published
2011
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5. Viral infection prevents diabetes by inducing regulatory T cells through NKT cell-plasmacytoid dendritic cell interplay

Author

Agnès Lehuen, Roberto Mallone, Marc Dalod, Lucie Beaudoin, Julien Diana, Anna Tafuri, Vedran Brezar, Christian Boitard, Andrew L. Mellor, Matthias von Herrath, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), 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), Medical College of Georgia, Immunotherapy Center, Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), La Jolla Institute for Immunology [La Jolla, CA, États-Unis], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), CHU Cochin [AP-HP], Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), La Jolla Institute for Allergy and Immunology (LIA), La Jolla Institute for Allergy & Immunology, Université Paris Descartes - Paris 5 ( UPD5 ), Centre d'Immunologie de Marseille - Luminy ( CIML ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and La Jolla Institute for Allergy and Immunology ( LIA )

Subjects
MESH: Interleukin-10, endocrine system diseases, Programmed Cell Death 1 Receptor, MESH: Membrane Glycoproteins, MESH : Membrane Glycoproteins, MESH: Lymph Nodes, Cell Communication, CD8-Positive T-Lymphocytes, Lymphocyte Activation, T-Lymphocytes, Regulatory, B7-H1 Antigen, MESH : Diabetes Mellitus, Type 1, MESH : T-Lymphocytes, Regulatory, Interleukin 21, Mice, 0302 clinical medicine, Transforming Growth Factor beta, immune system diseases, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, Cytotoxic T cell, MESH: Animals, IL-2 receptor, MESH : Antigens, CD80, MESH : Lymph Nodes, 0303 health sciences, Membrane Glycoproteins, MESH: Dendritic Cells, MESH : Peptides, MESH: Peptides, FOXP3, hemic and immune systems, MESH : CD8-Positive T-Lymphocytes, Natural killer T cell, MESH: CD8-Positive T-Lymphocytes, 3. Good health, Interleukin-10, MESH: Virus Diseases, medicine.anatomical_structure, Virus Diseases, Antigens, Surface, B7-1 Antigen, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Diabetes Mellitus, Type 1, MESH : Apoptosis Regulatory Proteins, MESH : Antigens, Surface, endocrine system, MESH : Cell Communication, MESH: Antigens, Surface, T cell, Immunology, macromolecular substances, Biology, Article, 03 medical and health sciences, Islets of Langerhans, MESH: Antigens, CD80, MESH : Interleukin-10, MESH : Mice, MESH: Cell Communication, medicine, Animals, MESH : Islets of Langerhans, Antigen-presenting cell, MESH: Lymphocyte Activation, MESH: Mice, MESH : Lymphocyte Activation, MESH: Transforming Growth Factor beta, 030304 developmental biology, MESH: Apoptosis Regulatory Proteins, MESH: T-Lymphocytes, Regulatory, MESH: Islets of Langerhans, Dendritic cell, Dendritic Cells, MESH : Virus Diseases, MESH : Natural Killer T-Cells, MESH : Transforming Growth Factor beta, Diabetes Mellitus, Type 1, MESH: Natural Killer T-Cells, MESH : Dendritic Cells, Natural Killer T-Cells, MESH : Animals, Lymph Nodes, Apoptosis Regulatory Proteins, Peptides, 030215 immunology
Abstract

iNKT cell and pDC cross talk prevents type 1 diabetes by inducing T reg cells in the pancreatic lymph node during viral infection., Type 1 diabetes (T1D) is an autoimmune disease resulting from T cell–mediated destruction of insulin-producing β cells, and viral infections can prevent the onset of disease. Invariant natural killer T cells (iNKT cells) exert a regulatory role in T1D by inhibiting autoimmune T cell responses. As iNKT cell–plasmacytoid dendritic cell (pDC) cooperation controls viral replication in the pancreatic islets, we investigated whether this cellular cross talk could interfere with T1D development during viral infection. Using both virus-induced and spontaneous mouse models of T1D, we show that upon viral infection, iNKT cells induce TGF-β–producing pDCs in the pancreatic lymph nodes (LNs). These tolerogenic pDCs convert naive anti-islet T cells into Foxp3+ CD4+ regulatory T cells (T reg cells) in pancreatic LNs. T reg cells are then recruited into the pancreatic islets where they produce TGF-β, which dampens the activity of viral- and islet-specific CD8+ T cells, thereby preventing T1D development in both T1D models. These findings reveal a crucial cooperation between iNKT cells, pDCs, and T reg cells for prevention of T1D by viral infection.

Published
2011
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6. μ-Opioid Receptor Is Induced by IL-13 within Lymph Nodes from Patients with Sézary Syndrome

Author

Jérôme Boué, Pierre Cavaillès, Laurence Lamant, Alan Bénard, Emmanuelle Chapey, Gilles Dietrich, Jagadeesh Bayry, Nicolas Meyer, Srini V. Kaveri, Catherine Blanpied, Pierre Brousset, Centre de Physiopathologie de Toulouse-Purpan (INSERM U563 - CNRS UMR1037), Centre National de la Recherche Scientifique (CNRS)-Centre de lutte contre le cancer (CLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Institut Claudius Regaud, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de dermatologie, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], CHU Toulouse [Toulouse]-Institut Claudius Regaud-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de lutte contre le cancer (CLCC)-Centre National de la Recherche Scientifique (CNRS), IFR150, Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Sorbonne Paris Cité (USPC), Institut National de la Santé et de la Recherche Médicale (INSERM), Bisanz, Cordelia, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut Claudius Regaud-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de lutte contre le cancer (CLCC)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Dermatologie [CHU Toulouse], Pôle Clinique des Voies respiratoires [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche-Santé (Université Pierre et Marie Curie), Centre de Physiopathologie Toulouse Purpan (ex IFR 30 et IFR 150), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR30-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), IFR150 ( Université Paul Sabatier ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] ( LAPM ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Centre National de la Recherche Scientifique ( CNRS ), Université Joseph Fourier - Grenoble 1 ( UJF ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Unité Mixte de Recherche-Santé ( Université Pierre et Marie Curie ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Departement of Dermatology ( CHU Purpan ), CHU Purpan, Service d'anatomie et cytologie pathologiques [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre de Recherche en Cancérologie de Toulouse ( CRCT ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service d'anatomie pathologique et histologie-cytologie [Rangueil], and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital de Rangueil

Subjects
CD4-Positive T-Lymphocytes, MESH: Interleukin-13, Skin Neoplasms, MESH : RNA, Messenger, Enkephalin, Biopsy, Receptors, Opioid, mu, Gene Expression, MESH: Lymph Nodes, CD8-Positive T-Lymphocytes, MESH: Monocytes, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Biochemistry, Monocytes, MESH: Biopsy, 0302 clinical medicine, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, Opioid receptor, polycyclic compounds, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Receptor, Lymph node, Cells, Cultured, MESH : Lymph Nodes, ComputingMilieux_MISCELLANEOUS, Endogenous opioid, MESH: Langerhans Cells, 0303 health sciences, Interleukin-13, MESH : Receptors, Opioid, mu, MESH: Dendritic Cells, MESH : Immune Tolerance, MESH: CD4-Positive T-Lymphocytes, MESH : CD8-Positive T-Lymphocytes, MESH: CD8-Positive T-Lymphocytes, 3. Good health, medicine.anatomical_structure, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH : CD4-Positive T-Lymphocytes, MESH: Sezary Syndrome, [SDV.IMM]Life Sciences [q-bio]/Immunology, Lymph, MESH: Cells, Cultured, MESH: Gene Expression, MESH: Immune Tolerance, [SDV.IMM] Life Sciences [q-bio]/Immunology, medicine.drug_class, MESH : Langerhans Cells, MESH: Receptors, Opioid, mu, Dermatology, Biology, 03 medical and health sciences, Immune system, MESH : Cells, Cultured, MESH : Interleukin-13, mental disorders, Immune Tolerance, medicine, Humans, Sezary Syndrome, RNA, Messenger, Opioid peptide, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Molecular Biology, 030304 developmental biology, MESH: RNA, Messenger, MESH : Sezary Syndrome, MESH: Humans, MESH: Skin Neoplasms, MESH : Skin Neoplasms, MESH : Humans, Dendritic Cells, Cell Biology, MESH : Gene Expression, MESH : Monocytes, nervous system, Langerhans Cells, MESH : Biopsy, MESH : Dendritic Cells, Immunology, Lymph Nodes, human activities, 030215 immunology
Abstract

International audience; Endogenous opioid peptides mainly produced by neurons are also released by immune cells. They bind to mu- (mu-opioid receptor, MOR), delta-, and kappa-opioid receptors. On the basis of studies on mice showing that MOR is the main mediator of the deleterious effects of opioids on immunity, we wondered whether MOR, absent under normal conditions, is expressed in some pathological situations such as lymphomas. mRNA expression for all three opioid receptors was examined in lymph node biopsy samples from patients with non-Hodgkin's B-cell and T-cell lymphomas. We found that MOR and one of its ligands (enkephalin) are simultaneously expressed almost exclusively in lymph nodes from patients with Sézary cutaneous T cell lymphoma. As MOR was undetectable in circulating malignant T lymphocytes and in normal immune cells, we hypothesized that tumor-released cytokines might induce MOR expression in non-neoplastic lymph node cells. The correlation between mRNA levels of MOR and interleukin-13 (IL-13) within lymph nodes from Sézary patients led us to investigate the ability of IL-13 to upregulate MOR expression in normal immune cell subsets. We found that IL-13 upregulates MOR in activated Langerhans cells. Thus, our data suggest that, under pathological conditions, IL-13 overexpression might allow immune-derived endogenous opioids to down-modulate immune response.

Published
2010
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7. Foxp3+ T cells induce perforin-dependent dendritic cell death in tumor-draining lymph nodes

Author

Tim Sparwasser, Alexandre Boissonnas, Luc Fetler, Alix Scholer-Dahirel, Bernard Malissen, Adrien Kissenpfennig, Luigia Pace, Fabien Valet, Virginie Simon-Blancal, Sebastian Amigorena, Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Hannover Medical School [Hannover] (MHH), Physico-Chimie-Curie (PCC), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut Curie-Université Pierre et Marie Curie - Paris 6 (UPMC), Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), MINES ParisTech - École nationale supérieure des mines de Paris-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE, Centre d'Immunologie de Marseille - Luminy ( CIML ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Hannover Medical School [Hannover] ( MHH ), Physico-Chimie-Curie ( PCC ), and Centre National de la Recherche Scientifique ( CNRS ) -INSTITUT CURIE-Université Pierre et Marie Curie - Paris 6 ( UPMC )

Subjects
MESH: Cell Death, MESH : Fibrosarcoma, Fibrosarcoma, Priming (immunology), MESH: Lymph Nodes, MESH: T-Lymphocyte Subsets, Lymphocyte Activation, T-Lymphocytes, Regulatory, MESH: Mice, Knockout, MESH : T-Lymphocytes, Regulatory, Interleukin 21, Mice, 0302 clinical medicine, Cell Movement, T-Lymphocyte Subsets, MESH : Cell Movement, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, Cytotoxic T cell, MESH : Female, MESH: Animals, MOLIMMUNO, MESH: Cell Movement, MESH : Lymph Nodes, Mice, Knockout, 0303 health sciences, Cell Death, MESH: Dendritic Cells, MESH: Fibrosarcoma, Forkhead Transcription Factors, hemic and immune systems, MESH : Mice, Transgenic, 3. Good health, MESH : Forkhead Transcription Factors, Infectious Diseases, medicine.anatomical_structure, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Cell Line, Tumor, MESH: Mice, Transgenic, T cell, Immunology, Mice, Transgenic, chemical and pharmacologic phenomena, MESH : Mice, Inbred C57BL, Biology, TREG CELLS, MESH: Cell Adhesion, 03 medical and health sciences, MESH: Mice, Inbred C57BL, MESH: Forkhead Transcription Factors, Cell Line, Tumor, MESH : Mice, medicine, Lymph node stromal cell, Cell Adhesion, MESH : Neoplasm Transplantation, Animals, MESH : Perforin, Antigen-presenting cell, MESH: Lymphocyte Activation, MESH: Mice, MESH : Lymphocyte Activation, 030304 developmental biology, MESH : Cell Line, Tumor, Perforin, MESH: T-Lymphocytes, Regulatory, Dendritic cell, Dendritic Cells, MESH : T-Lymphocyte Subsets, MESH: Perforin, Mice, Inbred C57BL, MESH : Cell Adhesion, CELLIMMUNO, MESH : Cell Death, MESH : Dendritic Cells, Cancer research, MESH : Mice, Knockout, MESH : Animals, Lymph Nodes, MESH: Female, CD8, Neoplasm Transplantation, MESH: Neoplasm Transplantation, 030215 immunology
Abstract

International audience; Regulatory T (Treg) cells limit the onset of effective antitumor immunity, through yet-ill-defined mechanisms. We showed the rejection of established ovalbumin (OVA)-expressing MCA101 tumors required both the adoptive transfer of OVA-specific CD8(+) T cell receptor transgenic T cells (OTI) and the neutralization of Foxp3(+) T cells. In tumor-draining lymph nodes, Foxp3(+) T cell neutralization induced a marked arrest in the migration of OTI T cells, increased numbers of dendritic cells (DCs), and enhanced OTI T cell priming. Using an in vitro cytotoxic assay and two-photon live microscopy after adoptive transfer of DCs, we demonstrated that Foxp3(+) T cells induced the death of DCs in tumor-draining lymph nodes, but not in the absence of tumor. DC death correlated with Foxp3(+) T cell-DC contacts, and it was tumor-antigen and perforin dependent. We conclude that Foxp3(+) T cell-dependent DC death in tumor-draining lymph nodes limits the onset of CD8(+) T cell responses.

Published
2010
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8. Skin and peripheral lymph node invariant NKT cells are mainly retinoic acid receptor-related orphan receptor (gamma)t+ and respond preferentially under inflammatory conditions

Author

Gérard Eberl, Kamel Benlagha, Jean-Marc Doisne, Nádia Duarte, Jean-Benoît Le Luduec, Latiffa Amniai, Chantal Bécourt, Immunologie, génétique et traitement des maladies métaboliques et du diabète (UMR_S 561), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Immunité infection vaccination (I2V), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Développement des Tissus Lymphoïdes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie, génétique et traitement des maladies métaboliques et du diabète ( UMR_S 561 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Immunité infection vaccination ( I2V ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR128-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon

Subjects
MESH: Nuclear Receptor Subfamily 1, Group F, Member 3, MESH: Inflammation, Receptors, Retinoic Acid, MESH: Interleukin-17, Retinoic acid, MESH: Lymph Nodes, C-C chemokine receptor type 6, MESH: Mice, Knockout, chemistry.chemical_compound, Mice, 0302 clinical medicine, MESH : Cell Proliferation, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, MESH: Animals, MESH : Lymph Nodes, Skin, Orphan receptor, Mice, Knockout, 0303 health sciences, education.field_of_study, Receptors, Thyroid Hormone, Interleukin-17, MESH: Galactosylceramides, MESH : Receptors, Thyroid Hormone, hemic and immune systems, Nuclear Receptor Subfamily 1, Group F, Member 3, Natural killer T cell, MESH : Receptors, Retinoic Acid, MESH : Epithelial Cells, MESH: Epithelial Cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Nuclear Receptor Subfamily 1, Group F, Member 3, Interleukin 17, MESH : Interleukin-6, Immunology, Population, Galactosylceramides, MESH : Interleukin-17, Biology, 03 medical and health sciences, Immune system, MESH: Skin, MESH: Cell Proliferation, MESH : Mice, MESH : Skin, Animals, MESH: Receptors, Thyroid Hormone, education, MESH: Mice, 030304 developmental biology, Cell Proliferation, MESH: Receptors, Retinoic Acid, Inflammation, MESH : Inflammation, Interleukin-6, Epithelial Cells, MESH : Natural Killer T-Cells, MESH: Interleukin-6, Retinoic acid receptor, MESH: Natural Killer T-Cells, chemistry, Cancer research, MESH : Mice, Knockout, Natural Killer T-Cells, MESH : Animals, Lymph Nodes, MESH : Galactosylceramides, 030215 immunology
Abstract

Lymph nodes (LNs) have been long considered as comprising few invariant NKT (iNKT) cells, and these cells have not been studied extensively. In this study, we unravel the existence of stable rather than transitional LN-resident NK1.1(-) iNKT cell populations. We found the one resident in peripheral LNs (PLNs) to comprise a major IL-17-producing population and to express the retinoic acid receptor-related orphan receptor (gamma)t (ROR(gamma)t). These cells respond to their ligand alpha-galactosylceramide (alpha-GalCer) in vivo by expanding dramatically in the presence of LPS, providing insight into how this rare population could have an impact in immune responses to infection. PLN-resident ROR(gamma)t(+) NK1.1(-) iNKT cells express concomitantly CCR6, the integrin alpha-chain alpha(E) (CD103), and IL-1R type I (CD121a), indicating that they might play a role in inflamed epithelia. Accordingly, skin epithelia comprise a major ROR(gamma)t(+) CCR6(+)CD103(+)CD121a(+) NK1.1(-) cell population, reflecting iNKT cell composition in PLNs. Importantly, both skin and draining PLN ROR(gamma)t(+) iNKT cells respond preferentially to inflammatory signals and independently of IL-6, indicating that they could play a nonredundant role during inflammation. Overall, our study indicates that ROR(gamma)t(+) iNKT cells could play a major role in the skin during immune responses to infection and autoimmunity.

Published
2009
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9. KBA.62: a useful marker for primary and metastatic melanomas

Author

Sophie Le Guellec, Philippe Rochaix, Paul Carle, Pierre Payoux, Séverine Valmary-Degano, Talal Al Saati, François Launay, Laurence Lamant, Serge Boulinguez, Frédéric Lauwers, Pierre Brousset, Cécile Pages, Laboratoire d'Anatomie Pathologique [Purpan], CHU Toulouse [Toulouse], Institut Claudius Regaud, CRLCC Institut Claudius Regaud, Plateau technique d'Histopathologie Expérimentale, Institut Claude de Préval (ICP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Service de dermatologie, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service de chirurgie plastique et maxillo-faciale, CHU Purpan, Toulouse, Service de Médecine Nucléaire [Toulouse], CHU Toulouse [Toulouse]-Hôpital Rangueil, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Laboratoire d'anatomie pathologique [Besancon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), Institut de Physique Nucléaire d'Orsay ( IPNO ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), Imagerie cérébrale et handicaps neurologiques, Université Paul Sabatier - Toulouse 3 ( UPS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'anatomie pathologique et histologie-cytologie [Rangueil], Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse]-Hôpital de Rangueil, Université Sciences et Technologies - Bordeaux 1, Centre de Recherche en Cancérologie de Toulouse ( CRCT ), and Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
MESH: Neoplasm Proteins, Pathology, Skin Neoplasms, MESH : Immunohistochemistry, MESH: Lymphatic Metastasis, MESH : S100 Proteins, MESH: Antigens, Neoplasm, MESH: Lymph Nodes, MESH : Antigens, Neoplasm, Metastasis, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Antibodies, Monoclonal, 030207 dermatology & venereal diseases, 0302 clinical medicine, MESH : Tumor Markers, Biological, Lymph node, Melanoma, MESH : Lymph Nodes, Micrometastasis, S100 Proteins, Antibodies, Monoclonal, MESH : Lymphatic Metastasis, Immunohistochemistry, 3. Good health, Neoplasm Proteins, medicine.anatomical_structure, 030220 oncology & carcinogenesis, MESH : Antibodies, Monoclonal, Lymphatic Metastasis, Lymph, MESH : Sensitivity and Specificity, MESH: S100 Proteins, Melanoma-Specific Antigens, medicine.medical_specialty, MESH: Melanoma, Sentinel lymph node, MESH : Melanoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Sensitivity and Specificity, Pathology and Forensic Medicine, 03 medical and health sciences, MESH : Neoplasm Proteins, Antigens, Neoplasm, medicine, Biomarkers, Tumor, Humans, Desmoplastic melanoma, MESH: Humans, business.industry, MESH: Skin Neoplasms, MESH : Skin Neoplasms, MESH : Humans, MESH : Melanoma-Specific Antigens, MESH: Immunohistochemistry, medicine.disease, MESH: Sensitivity and Specificity, MESH: Melanoma-Specific Antigens, MESH: Tumor Markers, Biological, Lymph Nodes, business
Abstract

International audience; We previously described a novel antimelanoma antibody, designated KBA.62. However, review of the literature showed that only a few studies have reported on this antibody. We report our experience in the diagnosis of melanoma using KBA.62 and its value in both primary and metastatic conditions. In addition to conventional melanomas, we included desmoplastic and spindle cell melanomas, whose diagnosis can be challenging. We also focus on identification of malignant cells in sentinel lymph node biopsies using KBA.62, by comparison with anti-S-100 protein and HMB-45 antibodies, because discrepancies in sensitivity and specificity of melanoma markers have given rise to numerous studies aiming to determine the best panel for the evaluation of sentinel lymph node from patients with melanoma. Overall, KBA.62 was positive in 93% of primary and metastatic melanomas. Interestingly, the 12 cases of desmoplastic and spindle cell melanomas had strongly positive results. In addition, the results of our study performed on a series of 215 sentinel lymph nodes showed that the sensitivity of anti-S-100 protein and KBA.62 antibodies in detecting occult metastasis was similar. Moreover, KBA.62 identified 6 patients (3%) who had confirmed sentinel lymph node metastasis but were negative for HMB-45. The resolution was higher with KBA.62 than that observed with anti-S-100 protein antibody, as the nonmelanocytic positive cells for KBA.62 in lymph nodes were only represented by endothelial cells, which therefore constituted an intrinsic positive control. We conclude that KBA.62 antibody is a useful additional marker for melanoma, specifically in desmoplastic/spindle cell cases and in the context of micrometastasis in sentinel lymph node.

Published
2008
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10. Plasmocytoid dendritic cell dynamics and alpha IFN production during Simian Immunodeficiency Virus infection with a nonpathogenic outcome

Author

Abdourahmane Faye, Désirée Kunkel, Michaela Müller-Trutwin, Beatrice Jacquelin, Mickaël J.-Y. Ploquin, Pierre Lebon, Anne Hosmalin, Lorenzo Mortara, Françoise Barré-Sinoussi, Cécile Butor, Ousmane M. Diop, Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Régulation des Infections Rétrovirales, Institut Pasteur [Paris], Service de virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Saint-Vincent de Paul, Université Paris Diderot - Paris 7 (UPD7), Institut Cochin (UMR_S567 / UMR 8104), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Institut Pasteur [Paris] (IP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Saint-Vincent de Paul, 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 de Dakar - Réseau International des Instituts Pasteur (RIIP), Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Saint-Vincent de Paul, and Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS)

Subjects
CD4-Positive T-Lymphocytes, MESH: Interleukin-12, Time Factors, Simian Acquired Immunodeficiency Syndrome, Cell Count, MESH: Lymph Nodes, Plasmacytoid dendritic cell, MESH : Cell Count, medicine.disease_cause, LN, 0302 clinical medicine, Chlorocebus aethiops, T-cell activation, MESH: Animals, MESH : Lymph Nodes, 0303 health sciences, MESH: Dendritic Cells, MESH : Simian Acquired Immunodeficiency Syndrome, MESH: CD4-Positive T-Lymphocytes, hemic and immune systems, Interleukin-12, 3. Good health, IL-12, MESH : CD4-Positive T-Lymphocytes, SIVagm, Interleukin 12, MESH : Interferon-alpha, [SDV.IMM]Life Sciences [q-bio]/Immunology, Simian Immunodeficiency Virus, MESH: Interferon-alpha, MESH: Simian Acquired Immunodeficiency Syndrome, medicine.drug, MESH : Time Factors, MESH: Simian immunodeficiency virus, PDC, MESH : Interleukin-6, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Alpha interferon, Viremia, macromolecular substances, Biology, Microbiology, 03 medical and health sciences, Virology, medicine, MESH : Interleukin-12, Animals, Interferon alfa, 030304 developmental biology, IL-6, Interleukin-6, MESH: Cell Count, MESH: Time Factors, TLR9, Interferon-alpha, Dendritic cell, Dendritic Cells, Simian immunodeficiency virus, medicine.disease, MESH: Cercopithecus aethiops, MESH: Interleukin-6, MESH : Simian immunodeficiency virus, Insect Science, MESH : Dendritic Cells, Pathogenesis and Immunity, MESH : Animals, MESH : Cercopithecus aethiops, Lymph Nodes, IFN-alpha, PDC, LN, IFN-alpha, SIVagm, IL-6, IL-12, T-cell activation, 030215 immunology
Abstract

We addressed the role of plasmacytoid dendritic cells (PDC) in protection against AIDS in nonpathogenic simian immunodeficiency virus (SIVagm) infection in African green monkeys (AGMs). PDC were monitored in blood and lymph nodes (LNs) starting from day 1 postinfection. We observed significant declines in blood during acute infection. However, PDC then returned to normal levels, and chronically infected AGMs showed no decrease of PDC in blood. There was a significant increase of PDC in LNs during acute infection. Blood PDC displayed only weak alpha interferon (IFN-α) responses to TLR9 agonist stimulation before infection. However, during acute infection, both blood and LN PDC showed a transiently increased propensity for IFN-α production. Bioactive IFN-α was detected in plasma concomitant with the peak of viremia, though levels were only low to moderate in some animals. Plasma interleukin 6 (IL-6) and IL-12 were not increased. In conclusion, PDC were recruited to the LNs and displayed increased IFN-α production during acute infection. However, increases in IFN-α were transient. Together with the lack of inflammatory cytokine responses, these events might play an important role in the low level of T-cell activation which is associated with protection against AIDS in nonpathogenic SIVagm infection.

Published
2008
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11. HHV-6 and EBV DNA quantitation in lymph nodes of 86 patients with Hodgkin's lymphoma

Author

Christophe Piguet, Dominique Bordessoule, Arnaud Jaccard, Christine Rouzioux, Barbara Petit, Sylvie Ranger-Rogez, Aurélie Lacroix, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Laboratoire de Virologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pédiatrie médicale - Spécialités médicales [CHU Limoges], Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], Université de Limoges (UNILIM), Université de Limoges (UNILIM) - Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503) - Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Necker - Enfants Malades [AP-HP]

Subjects
Male, Herpesvirus 4, Human, viruses, Herpesvirus 6, Human, MESH : Aged, MESH : Herpesviridae Infections, MESH: Lymph Nodes, MESH: Herpesviridae Infections, medicine.disease_cause, MESH : Herpesvirus 6, Human, 0302 clinical medicine, MESH: Aged, 80 and over, MESH : Child, hemic and lymphatic diseases, MESH: Child, MESH : Hodgkin Disease, Gammaherpesvirinae, MESH : Female, MESH : Viral Matrix Proteins, MESH : DNA, Viral, Child, Lymph node, MESH : Lymph Nodes, MESH: Aged, Aged, 80 and over, 0303 health sciences, MESH: Middle Aged, MESH: Follow-Up Studies, Herpesviridae Infections, MESH : Adult, Middle Aged, MESH : Herpesvirus 4, Human, Hodgkin Disease, MESH: Hodgkin Disease, 3. Good health, Infectious Diseases, medicine.anatomical_structure, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Human herpesvirus 6, Female, Adult, [SDV.IMM] Life Sciences [q-bio]/Immunology, Adolescent, MESH : Male, Biology, Virus, Herpesviridae, Viral Matrix Proteins, 03 medical and health sciences, Virology, MESH : Adolescent, medicine, Humans, MESH : Middle Aged, MESH : Aged, 80 and over, 030304 developmental biology, Aged, MESH: Adolescent, MESH: Viral Matrix Proteins, MESH: Humans, MESH : Humans, MESH : Follow-Up Studies, MESH: Adult, MESH: Herpesvirus 4, Human, medicine.disease, Hodgkin's lymphoma, biology.organism_classification, MESH: Herpesvirus 6, Human, Epstein–Barr virus, MESH: Male, Lymphoma, MESH: DNA, Viral, Immunology, DNA, Viral, Lymph Nodes, MESH: Female, Follow-Up Studies
Abstract

International audience; Human herpesvirus (HHV-6) and Epstein-Barr virus (EBV), are two ubiquitous human herpesviruses which share many common features although they belong to different sub-families. In particular, both viruses are found in lymph nodes of patients suffering from Hodgkin's lymphoma. The aim of this study was to detect and to quantify independently HHV-6 and EBV by a real-time PCR in lymph nodes from 86 patients with Hodgkin's lymphoma. EBV quantitative method was compared with LMP-1 protein detection among the same samples. EBV genome was detected for 61.6% of the patients (53/86) and the highest prevalence of this virus was observed in Hodgkin's lymphoma with mixed-cellularity histopathological type (80%). In contrast to that, HHV-6 genome was detected for 79.1% of the patients (68/86) and was most observed in the nodular-sclerosis group (83.6%). Among the 68 HHV-6 positive samples, 63 belonged to the B subtype. A large number of biopsies (47.7%) were positive for both viruses whereas a little number (7%) was negative for both. EBV quantitation and LMP-1 immunohistochemistry were correlated statistically but this latter technique was less sensitive. Among the nodular-sclerosis patients, HHV-6-/EBV+ patients were significatively older than HHV-6+/EBV- patients. Patients infected dually had higher values of quantitation for each virus than those positive for one virus. Data of the clinical follow-up obtained by diagnosis and during the treatment of 83 patients, were correlated with the virological findings.

Published
2007
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12. Angiopoietin-like 4 prevents metastasis through inhibition of vascular permeability and tumor cell motility and invasiveness

Author

Stéphane Germain, Emmanuelle Le Coz, Lluis M. Mir, Josette Philippe, H. Mekid, Ariane Galaup, Elisabeth Connault, Catherine Monnot, Aurélie Cazes, Pierre Corvol, Paule Opolon, Sébastien Le Jan, Pathologie vasculaire et endocrinologie rénale - Chaire de médecine expérimentale (INSERM U36), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM), Vectorologie et transfert de gènes (VTG / UMR8121), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie A [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Germain, Stéphane, Pathologie vasculaire et endocrinologie rénale, Collège de France ( CdF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Vectorologie et transfert de gènes ( VTG / UMR8121 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Centre National de la Recherche Scientifique ( CNRS ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP )

Subjects
MESH : Mice, I, Lung Neoplasms, MESH: Lymphatic Metastasis, Melanoma, Experimental, Vascular permeability, MESH: Lymph Nodes, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Metastasis, Carcinoma, Lewis Lung, Mice, 0302 clinical medicine, Cell Movement, MESH : Cell Movement, MESH : Female, MESH: Animals, Neoplasm Metastasis, MESH: Cell Movement, MESH : Lymph Nodes, 0303 health sciences, MESH : Melanoma, Experimental, Multidisciplinary, MESH: Carcinoma, Lewis Lung, biology, Lymphopoiesis, MESH : Lymphatic Metastasis, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Biological Sciences, Vinculin, MESH: Lymphopoiesis, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH: Melanoma, Experimental, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Intercellular Signaling Peptides and Proteins, Female, Stress fiber, MESH: Cell Line, Tumor, MESH : Lymphopoiesis, Neovascularization, Physiologic, [SDV.CAN]Life Sciences [q-bio]/Cancer, Angiopoietin-like 4 Protein, Capillary Permeability, Angiopoietin, MESH: Mice, I, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH : Carcinoma, Lewis Lung, Cell Line, Tumor, MESH : Mice, medicine, Angiopoietin-Like Protein 4, Animals, Humans, Neoplasm Invasiveness, MESH : Lung Neoplasms, MESH: Intercellular Signaling Peptides and Proteins, MESH : Capillary Permeability, MESH: Mice, MESH : Intercellular Signaling Peptides and Proteins, 030304 developmental biology, MESH: Humans, MESH : Cell Line, Tumor, MESH : Humans, Intravasation, MESH: Capillary Permeability, Actin cytoskeleton, medicine.disease, MESH: Lung Neoplasms, Mice, Inbred C57BL, biology.protein, Cancer research, MESH : Animals, Lymph Nodes, Angiopoietins, MESH: Female
Abstract

Angiopoietin-like 4 (ANGPTL4), a secreted protein of the angiopoietin-like family, is induced by hypoxia in both tumor and endothelial cells as well as in hypoxic perinecrotic areas of numerous cancers. Here, we investigated whether ANGPTL4 might affect tumor growth as well as metastasis. Metastatic 3LL cells were therefore xenografted into control mice and mice in which ANGPTL4 was expressed by using in vivo DNA electrotransfer. Whereas primary tumors grew at a similar rate in both groups, 3LL cells metastasized less efficiently to the lungs of mice that expressed ANGPTL4. Fewer 3LL emboli were observed in primary tumors, suggesting that intravasation of 3LL cells was inhibited by ANGPTL4. Furthermore, melanoma B16F0 cells injected into the retro-orbital sinus also metastasized less efficiently in mice expressing ANGPTL4. Although B16F0 cells were observed in lung vessels, they rarely invaded the parenchyma, suggesting that ANGPTL4 affects extravasation. In addition, recombinant B16F0 cells that overexpress ANGPTL4 were generated, showing a lower capacity for in vitro migration, invasion, and adhesion than control cells. Expression of ANGPTL4 induced reorganization of the actin cytoskeleton through inhibition of actin stress fiber formation and vinculin localization at focal contacts. Together, these results show that ANGPTL4, through its action on both vascular and tumor compartments, prevents the metastatic process by inhibiting vascular activity as well as tumor cell motility and invasiveness.

Published
2006
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13. Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes

Author

Ronald N. Germain, Frédéric Brau, Nicolas Glaichenhaus, Jackson G. Egen, Lily Koo, Marc Bajénoff, Jean Pierre Laugier, Lymphocyte Biology Section ( NIAID ), National Institutes of Health, Immunologie des Maladies Infectieuses Allergiques et Autoimmunes, Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Commun de Microscopie Appliquée ( CCMA ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ), Institut de pharmacologie moléculaire et cellulaire ( IPMC ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Intramural Research Program of NIAID, NIH, DHHS, Institut de la Santé et de la Recherche Médicale (INSERM), Lymphocyte Biology Section (NIAID), Université Nice Sophia Antipolis (... - 2019) (UNS), 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), Centre Commun de Microscopie Appliquée (CCMA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Institut de pharmacologie moléculaire et cellulaire (IPMC), 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
Pathology, Adoptive cell transfer, Lymphocyte, MESH : Immunohistochemistry, MESH : Diagnostic Imaging, MESH : Lymphocytes, MESH: Chemotaxis, Leukocyte, MESH: Lymph Nodes, Cell Communication, Mice, 0302 clinical medicine, Reticular cell, MESH: Microscopy, Confocal, Immunology and Allergy, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, Lymphocytes, MESH : Lymph Nodes, 0303 health sciences, Microscopy, Confocal, MESH : Adoptive Transfer, Cell migration, MESH : Chemotaxis, Leukocyte, Adoptive Transfer, Immunohistochemistry, Cell biology, Chemotaxis, Leukocyte, medicine.anatomical_structure, Infectious Diseases, MESH : Microscopy, Electron, Transmission, MESH: Microscopy, Electron, Transmission, [SDV.IMM]Life Sciences [q-bio]/Immunology, Diagnostic Imaging, MESH : Microscopy, Electron, Scanning, medicine.medical_specialty, Stromal cell, Naive T cell, MESH: Microscopy, Electron, Scanning, MESH : Cell Communication, T cell, Immunology, MESH : Mice, Inbred C57BL, Biology, 03 medical and health sciences, Microscopy, Electron, Transmission, MESH: Mice, Inbred C57BL, MESH: Cell Communication, MESH : Mice, medicine, Animals, MESH : Microscopy, Confocal, MESH: Mice, 030304 developmental biology, Follicular dendritic cells, MESH: Diagnostic Imaging, MESH: Immunohistochemistry, Mice, Inbred C57BL, MESH: Adoptive Transfer, CELLIMMUNO, MESH : Stromal Cells, Microscopy, Electron, Scanning, CELLBIO, MESH: Lymphocytes, Lymph Nodes, MESH : Animals, Stromal Cells, MESH: Stromal Cells, 030215 immunology
Abstract

SummaryAfter entry into lymph nodes (LNs), B cells migrate to follicles, whereas T cells remain in the paracortex, with each lymphocyte type showing apparently random migration within these distinct areas. Other than chemokines, the factors contributing to this spatial segregation and to the observed patterns of lymphocyte movement are poorly characterized. By combining confocal, electron, and intravital microscopy, we showed that the fibroblastic reticular cell network regulated naive T cell access to the paracortex and also supported and defined the limits of T cell movement within this domain, whereas a distinct follicular dendritic cell network similarly served as the substratum for movement of follicular B cells. These results highlight the central role of stromal microanatomy in orchestrating cell migration within the LN.

Published
2006
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14. Natural killer cell behavior in lymph nodes revealed by static and real-time imaging

Author

Béatrice Breart, Hai Qi, Veronique M. Braud, Marc Bajénoff, Ronald N. Germain, Alex Yee-Chen Huang, Nicolas Glaichenhaus, Julie Cazareth, Institut de pharmacologie moléculaire et cellulaire ( IPMC ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), National Institutes of Health, Bethesda ( NIH ), National Institutes of Health ( NIH ), Université Côte d'Azur ( UCA ), Immunologie des Maladies Infectieuses Allergiques et Autoimmunes, Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), 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), National Institutes of Health, Bethesda (NIH), National Institutes of Health [Bethesda] (NIH), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), and 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)

Subjects
CD4-Positive T-Lymphocytes, MESH: Signal Transduction, MESH: Inflammation, Cellular differentiation, MESH : Immunohistochemistry, MESH: Lymph Nodes, MESH : Leishmaniasis, Cutaneous, Lymphocyte Activation, Mice, Interleukin 21, 0302 clinical medicine, MESH: Leishmania major, Immunology and Allergy, Interferon gamma, MESH: Animals, MESH : Lymph Nodes, Leishmania major, Mice, Inbred BALB C, 0303 health sciences, MESH: CD4-Positive T-Lymphocytes, Cell Differentiation, MESH : Interferon Type II, Articles, Acquired immune system, Immunohistochemistry, MESH : Mice, Transgenic, Cell biology, Killer Cells, Natural, medicine.anatomical_structure, MESH : CD4-Positive T-Lymphocytes, MESH : Killer Cells, Natural, MESH : Cell Differentiation, Intravital microscopy, Signal Transduction, medicine.drug, MESH: Cell Differentiation, MESH: Killer Cells, Natural, MESH: Mice, Transgenic, MESH: Interferon Type II, T cell, Immunology, MESH: Mice, Inbred BALB C, Leishmaniasis, Cutaneous, Mice, Transgenic, Biology, Article, Natural killer cell, MESH : Leishmania major, Interferon-gamma, 03 medical and health sciences, MESH : Microscopy, Fluorescence, Multiphoton, MESH : Mice, medicine, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Lymphocyte Activation, MESH: Mice, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Lymphocyte Activation, MESH : Mice, Inbred BALB C, 030304 developmental biology, Inflammation, MESH : Signal Transduction, MESH: Humans, MESH : Inflammation, MESH : Humans, MESH: Immunohistochemistry, Dendritic cell, Cell Biology, MESH: Leishmaniasis, Cutaneous, Microscopy, Fluorescence, Multiphoton, MESH: Microscopy, Fluorescence, Multiphoton, Lymph Nodes, MESH : Animals, 030215 immunology
Abstract

Natural killer (NK) cells promote dendritic cell (DC) maturation and influence T cell differentiation in vitro. To better understand the nature of the putative interactions among these cells in vivo during the early phases of an adaptive immune response, we have used immunohistochemical analysis and dynamic intravital imaging to study NK cell localization and behavior in lymph nodes (LNs) in the steady state and shortly after infection with Leishmania major. In the LNs of naive mice, NK cells reside in the medulla and the paracortex, where they closely associate with DCs. In contrast to T cells, intravital microscopy revealed that NK cells in the superficial regions of LNs were slowly motile and maintained their interactions with DCs over extended times in the presence or absence of immune-activating signals. L. major induced NK cells to secrete interferon-γ and to be recruited to the paracortex, where concomitant CD4 T cell activation occurred. Therefore, NK cells form a reactive but low mobile network in a strategic area of the LN where they can receive inflammatory signals, interact with DCs, and regulate colocalized T cell responses.

Published
2006
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15. More About the 'Heterogeneity' of Merkel Cell Carcinoma

Author

Pablo Ortega-Deballon, Claire Chalumeau, Service de Chirurgie Digestive, Cancérologique, Générale, Endocrinienne et Urgences (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Ortega Deballon, Pablo, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer (U866) (LNC), and Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)

Subjects
medicine.medical_specialty, Pathology, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, MESH : Aged, MESH: Lymph Nodes, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, medicine, MESH : Axilla, MESH : Female, MESH : Carcinoma, Merkel Cell, [ SDV.MHEP.CHI ] Life Sciences [q-bio]/Human health and pathology/Surgery, ComputingMilieux_MISCELLANEOUS, MESH : Lymph Nodes, MESH: Aged, MESH: Humans, Merkel cell carcinoma, business.industry, MESH: Skin Neoplasms, MESH : Humans, MESH : Skin Neoplasms, MESH: Carcinoma, Merkel Cell, medicine.disease, Surgery, Axilla, medicine.anatomical_structure, MESH: Axilla, business, MESH: Female
Abstract

International audience

Published
2010
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