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16 results on '"MESH: Lymphopenia"'

1. Fine Analysis of Lymphocyte Subpopulations in SARS-CoV-2 Infected Patients: Differential Profiling of Patients With Severe Outcome

Author

Giovanna Clavarino, Corentin Leroy, Olivier Epaulard, Tatiana Raskovalova, Antoine Vilotitch, Martine Pernollet, Chantal Dumestre-Pérard, Federica Defendi, Marion Le Maréchal, Audrey Le Gouellec, Pierre Audoin, Jean-Luc Bosson, Pascal Poignard, Matthieu Roustit, Marie-Christine Jacob, Jean-Yves Cesbron, Centre Hospitalier Universitaire [Grenoble] (CHU), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Service de Biochimie Biologie Moléculaire et Toxicologie Environnementale, Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), and Université Grenoble Alpes (UGA)

Subjects
lymphocytes, CD4-Positive T-Lymphocytes, B-Lymphocytes, MESH: Humans, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], SARS-CoV-2, flow cytometry, Immunology, MESH: Lymphocyte Subsets, MESH: CD4-Positive T-Lymphocytes, COVID-19, CD8-Positive T-Lymphocytes, Lymphocyte Activation, MESH: CD8-Positive T-Lymphocytes, Lymphocyte Subsets, MESH: Lymphopenia, MESH: B-Lymphocytes, Lymphopenia, Immunology and Allergy, MESH: COVID-19, Humans, disease severity, MESH: SARS-CoV-2, MESH: Lymphocyte Activation
Abstract

COVID-19 is caused by the human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in widespread morbidity and mortality. CD4+ T cells, CD8+ T cells and neutralizing antibodies all contribute to control SARS-CoV-2 infection. However, heterogeneity is a major factor in disease severity and in immune innate and adaptive responses to SARS-CoV-2. We performed a deep analysis by flow cytometry of lymphocyte populations of 125 hospitalized SARS-CoV-2 infected patients on the day of hospital admission. Five clusters of patients were identified using hierarchical classification on the basis of their immunophenotypic profile, with different mortality outcomes. Some characteristics were observed in all the clusters of patients, such as lymphopenia and an elevated level of effector CD8+CCR7- T cells. However, low levels of T cell activation are associated to a better disease outcome; on the other hand, profound CD8+ T-cell lymphopenia, a high level of CD4+ and CD8+ T-cell activation and a high level of CD8+ T-cell senescence are associated with a higher mortality outcome. Furthermore, a cluster of patient was characterized by high B-cell responses with an extremely high level of plasmablasts. Our study points out the prognostic value of lymphocyte parameters such as T-cell activation and senescence and strengthen the interest in treating the patients early in course of the disease with targeted immunomodulatory therapies based on the type of adaptive response of each patient.

Published
2022

2. Angiotensin II induces reactive oxygen species, DNA damage, and T-cell apoptosis in severe COVID-19

Author

Lucy Kundura, Sandrine Gimenez, Renaud Cezar, Sonia André, Mehwish Younas, Yea-Lih Lin, Pierre Portalès, Claire Lozano, Charlotte Boulle, Jacques Reynes, Thierry Vincent, Clément Mettling, Philippe Pasero, Laurent Muller, Jean-Yves Lefrant, Claire Roger, Pierre-Géraud Claret, Sandra Duvnjak, Paul Loubet, Albert Sotto, Tu-Anh Tran, Jérôme Estaquier, Pierre Corbeau, Institut de génétique humaine (IGH), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Initial MAnagement and prevention of acute orGan failures IN critically ill patiEnts (IMAGINE), Université de Montpellier (UM), Laboratoire de Bioingénierie et NanoSciences (LBN), Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Virulence Bactérienne et Infections Chroniques (VBIC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU de Québec–Université Laval, Université Laval [Québec] (ULaval), and ANR-21-COVR-0024,ACT-LONG-COVID,Caractérisation clinique et biologique du syndrome d'activation mastocytaire dans le COVID long et prédisposition génétique(2021)

Subjects
T-Lymphocytes, Immunology, ACE2, Apoptosis, MESH: Lymphopenia, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Lymphopenia, Humans, MESH: COVID-19, Immunology and Allergy, MESH: SARS-CoV-2, DNA oxidation, Programmed cell death, MESH: DNA Damage, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Humans, SARS-CoV-2, Angiotensin II, COVID-19, MESH: Reactive Oxygen Species, MESH: T-Lymphocytes, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Oxidative stress, Angiotensin II receptor, MESH: Angiotensin II, MESH: Apoptosis COVID-19, Antioxidant, Reactive Oxygen Species, DNA Damage
Abstract

International audience; Background: Lymphopenia is predictive of survival in patients with coronavirus disease 2019 (COVID-19).Objective: The aim of this study was to understand the cause of the lymphocyte count drop in severe forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.Methods: Monocytic production of reactive oxygen species (ROSs) and T-cell apoptosis were measured by flow cytometry, DNA damage in PBMCs was measured by immunofluorescence, and angiotensin II (AngII) was measured by ELISA in patients infected with SARS-CoV-2 at admission to an intensive care unit (ICU) (n 5 29) or not admitted to an ICU (n 5 29) and in ageand sex-matched healthy controls.Results: We showed that the monocytes of certain patients with COVID-19 spontaneously released ROSs able to induce DNA damage and apoptosis in neighboring cells. Of note, high ROS production was predictive of death in ICU patients. Accordingly, in most patients, we observed the presence of DNA damage in up to 50% of their PBMCs and T-cell apoptosis. Moreover, the intensity of this DNA damage was linked to lymphopenia. SARS-CoV-2 is known to induce the internalization of its receptor, angiotensin-converting enzyme 2, which is a protease capable of catabolizing AngII. Accordingly, in certain patients with COVID-19 we observed high plasma levels of AngII. When looking for the stimulus responsible for their monocytic ROS production, we revealed that AngII triggers ROS production by monocytes via angiotensin receptor I. ROSs released by AngII-activated monocytes induced DNA damage and apoptosis in neighboring lymphocytes.Conclusion: We conclude that T-cell apoptosis provoked via DNA damage due to the release of monocytic ROSs could play a major role in COVID-19 pathogenesis.

Published
2022

3. Progressive Multifocal Leukoencephalopathy in Primary Immunodeficiencies

Author

Hadjadj, Jérôme, Guffroy, Aurélien, Delavaud, Christophe, Taieb, Guillaume, Meyts, Isabelle, Fresard, Anne, Streichenberger, Nathalie, L’honneur, Anne-Sophie, Rozenberg, Flore, Aguilar, Claire, Rosain, Jérémie, Picard, Capucine, Mahlaoui, Nizar, Lecuit, Marc, Hermine, Olivier, Lortholary, Olivier, Suarez, Felipe, D'Aveni, Maud, Notarantonio, Anne, Bertrand, Allan, Boulangé, Laura, Pochon, Cécile, Rubio, Marie, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Référence National des Maladies Auto-Immunes Systémique Rares, CHU Strasbourg, Département de neurologie [Montpellier], Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University Hospitals Leuven [Leuven], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Institut NeuroMyoGène (INMG), 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), Service de Virologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des Maladies infectieuses et tropicales [CHU Necker], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP]-Institut des Maladies Génétiques Imagine [Paris], Institut des Maladies Génétiques Imagine [Paris], Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)

Subjects
0301 basic medicine, Male, MESH: Immunotherapy, medicine.medical_treatment, viruses, [SDV]Life Sciences [q-bio], T-Lymphocytes, Azathioprine, 0302 clinical medicine, Demyelinating disease, Immunology and Allergy, ComputingMilieux_MISCELLANEOUS, B-Lymphocytes, MESH: Middle Aged, Progressive multifocal leukoencephalopathy, Leukoencephalopathy, Progressive Multifocal, virus diseases, Immunosuppression, Middle Aged, JC Virus, 3. Good health, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, MESH: Young Adult, combined immunodeficiencies, [SDV.IMM]Life Sciences [q-bio]/Immunology, Rituximab, Female, MESH: Rituximab, Immunotherapy, medicine.drug, primary immunodeficiencies, Adult, medicine.medical_specialty, MESH: Immunologic Deficiency Syndromes, Adolescent, Immunology, immunosuppressive therapy, MESH: JC Virus, polyomavirus JC, MESH: Lymphopenia, 03 medical and health sciences, Combined immunodeficiencies, Young Adult, MESH: B-Lymphocytes, Lymphopenia, medicine, Humans, MESH: Azathioprine, Retrospective Studies, MESH: Adolescent, MESH: Humans, business.industry, Tumor Necrosis Factor-alpha, MESH: Leukoencephalopathy, Progressive Multifocal, Immunologic Deficiency Syndromes, Retrospective cohort study, MESH: Adult, MESH: Retrospective Studies, medicine.disease, Dermatology, MESH: Male, 030104 developmental biology, MESH: T-Lymphocytes, MESH: Tumor Necrosis Factor-alpha, Complication, business, MESH: Female, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Purpose:Progressive multifocal leukoencephalopathy (PML) is a rare but severe demyelinating disease caused by the polyoma-virus JC (JCV) in immunocompromised patients. We report a series of patients with primary immune deficiencies (PIDs) who developed PML. Methods:Retrospective observational study including PID patients with PML. Clinical, immunological, imaging features, and outcome are provided for each patient. Results:Eleven unrelated patients with PIDs developed PML. PIDs were characterized by a wide range of syndromic or genetically defined defects, mostly with combined B and T cell impairment. Genetic diagnosis was made in 7 patients. Before the development of PML, 10 patients had recurrent infections, 7 had autoimmune and/or inflammatory manifestations, and 3 had a history of malignancies. Immunologic investigations showed CD4 + lymphopenia (median 265, range 50-344) in all cases. Six patients received immunosuppressive therapy in the year before PML onset, including prolonged steroid therapy in 3 cases, rituximab in 5 cases, anti-TNF-α therapy, and azathioprine in 1 case each. Despite various treatments, all but 1 patient died after a median of 8 months following PML diagnosis. Conclusion: PML is a rare but fatal complication of PIDs. Many cases are secondary to immunosuppressive therapy warranting careful evaluation before initiation subsequent immunosuppression during PIDs.

Published
2018

4. CD4 lymphopenia to identify end-of-life metastatic cancer patients

Author

Inthidar Labidi Galy, Catherine Sebban, Jean-Yves Blay, Olivier Tredan, Thomas Bachelot, Christophe Borg, Gilles Clapisson, Irène Philip, Claire Cropet, David Pérol, Isabelle Ray-Coquard, Pierre Biron, Sylvie Chabaud, Christine Ménétrier-Caux, Philippe A. Cassier, Christophe Caux, Julien Péron, Saas, Philippe, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Centre Léon Bérard [Lyon], Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), and Equipe 11

Subjects
CD4-Positive T-Lymphocytes, Male, Oncology, Cancer Research, Multivariate analysis, MESH: CD4 Lymphocyte Count, medicine.medical_treatment, Lymphocyte, MESH: Aged, 80 and over, 0302 clinical medicine, Neoplasms, MESH: Neoplasms, MESH: Incidence, Neoplasm Metastasis, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, Incidence, Incidence (epidemiology), MESH: CD4-Positive T-Lymphocytes, Middle Aged, Prognosis, 3. Good health, Survival Rate, medicine.anatomical_structure, MESH: Survival Analysis, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Survival Rate, MESH: Prognosis, MESH: Lymphopenia, 03 medical and health sciences, Lymphopenia, Internal medicine, medicine, Humans, Survival rate, Survival analysis, Aged, Chemotherapy, MESH: Humans, business.industry, Cancer, medicine.disease, Survival Analysis, MESH: Neoplasm Metastasis, MESH: Male, CD4 Lymphocyte Count, Surgery, business, MESH: Female, CD8, 030215 immunology
Abstract

International audience; BACKGROUND: Cancer patients with CD4 lymphopenia have an increased risk of severe toxicity after administration of cytotoxic chemotherapy. The impact of CD4 lymphopenia on long term overall survival (OS) of cancer patients was explored in this work. PATIENTS AND METHODS: The first prospective series (test series) included 219 patients with solid tumours, lymphomas or myelomas receiving chemotherapy within an oncology department in 1999 and 2000. A phenotypic analysis of lymphocyte subsets by flow cytometry was performed before chemotherapy on day 1. The prognostic value of total, CD4, CD8 and CD56 lymphocyte count for OS was tested in a multivariate analysis. The prognostic value of low CD4 counts was then tested in a validation series of 269 patients with metastatic solid tumours in second line treatment included in a prospective observational study in the Centre Leon Berard. RESULTS: In the test series, all patients with metastatic cancers and CD4 lymphopenia ≤ 200/μL (12% of metastatic patients) died within 18 months with a median OS of 5.9 months. CD4 count was an independent prognostic factor for OS and PFS in multivariate analysis. In the validation series, 83 (30%) of patients had CD4 count ≤ 200/μL: their median overall survival was 3.9 months with an 18-month survival rate of 6%. CD4 count was also an independent prognostic factor for overall survival in this series. CONCLUSIONS: CD4 lymphopenia

Published
2013

5. Lymphopenia in early arthritis: Impact on diagnosis and 3-year outcomes (ESPOIR cohort)

Author

Sandrine Jousse-Joulin, Divi Cornec, Alain Saraux, Carole Duquenne, Stephan Pavy, Valérie Devauchelle-Pensec, Thierry Marhadour, Alain Cantagrel, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Service de rhumatologie, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), and Centre d'Investigation Clinique (CIC - Brest)

Subjects
Male, medicine.medical_specialty, Early inflammatory joint disease, [SDV]Life Sciences [q-bio], Arthritis, Azathioprine, MESH: Arthritis, MESH: Lymphopenia, Rheumatology, immune system diseases, Internal medicine, Lymphopenia, Diagnosis, medicine, Prevalence, Rheumatoid factor, Humans, Longitudinal Studies, Prospective Studies, Rheumatoid arthritis, MESH: Longitudinal Studies, MESH: Prevalence, 2. Zero hunger, Cytopenia, Systemic lupus erythematosus, MESH: Humans, MESH: Middle Aged, business.industry, Middle Aged, medicine.disease, Prognosis, MESH: Male, MESH: Prospective Studies, 3. Good health, MESH: France, Hematologic disease, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Cohort, Immunology, Female, France, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract

Objectives In patients with early arthritis naive to disease-modifying antirheumatic drugs, we evaluated the prevalence of initial and persistent lymphopenia, underlying diagnoses, and risk of infection or malignancy. Methods Eight hundred and thirteen patients with early arthritis included in the ESPOIR cohort had a clinical examination, laboratory tests (viral serology, immunological tests, and cytokine profile), and radiographs. We determined the prevalence of lymphopenia at baseline and after 3 years, associated factors, diagnoses, and risk of infection or malignancy. Results At baseline, 50/813 (6.2%) patients had lymphopenia. Lymphopenia was associated with positive rheumatoid factor (P = 0.02), cytopenia (P ≤ 0.05), hepatitis C (P = 0.05), higher C-reactive protein and DAS28 (P ≤ 0.05 for both). Cytokine profile and radiological progression were not significantly different between patients with and without lymphopenia. Suspected diagnoses at inclusion were rheumatoid arthritis (RA, n = 27), unclassified arthritis (n = 15), systemic lupus erythematosus (SLE, n = 3), spondyloarthritis (n = 2), Sjogren's syndrome (n = 1), hematologic disease (n = 1), and fibromyalgia (n = 1). Fifteen patients out of 42 (35.7%) with initial lymphopenia had persistent lymphopenia after 3 years, including 5 with documented causes (lupus, hepatitis C, undernutrition, azathioprine, and tamoxifen); none had PVB19, HIV, or HBV infection and none experienced infections, solid or hematologic malignancies during follow-up. Final diagnoses in these 15 patients were RA (n = 6), unclassified arthritis (n = 6), SLE (n = 1), spondyloarthritis (n = 1), and fibromyalgia (n = 1). Conclusions Lymphopenia is rare in early arthritis. The most common rheumatic cause is RA, in which marked inflammation and other cytopenias are common. Lymphopenia in early arthritis is often short-lived, even when methotrexate is prescribed.

Published
2015

6. Homeostasis of Peripheral CD4+ T Cells: IL-2Rα and IL-2 Shape a Population of Regulatory Cells That Controls CD4+ T Cell Numbers

Author

Martine Papiernik, Afonso R. M. Almeida, Antonio A. Freitas, Nicolas Legrand, Biologie des Populations Lymphocytaires, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], 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] (IP)-Centre National de la Recherche Scientifique (CNRS), 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 ), Other departments, and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
CD4-Positive T-Lymphocytes, MESH: Adjuvants, Immunologic, MESH: T-Lymphocyte Subsets, MESH: Mice, Knockout, MESH : Radiation Chimera, Mice, Interleukin 21, 0302 clinical medicine, T-Lymphocyte Subsets, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Homeostasis, Immunology and Allergy, Cytotoxic T cell, MESH: Animals, IL-2 receptor, MESH: Bone Marrow Transplantation, MESH : Lymphocyte Count, Bone Marrow Transplantation, Mice, Knockout, 0303 health sciences, MESH : Interphase, ZAP70, MESH: CD4-Positive T-Lymphocytes, CD28, Natural killer T cell, Cell biology, MESH: Homeostasis, MESH : CD4-Positive T-Lymphocytes, MESH : Homeostasis, Radiation Chimera, MESH: Survival Analysis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Lymphopenia, MESH: Lymphocyte Count, MESH: Radiation Chimera, Immunology, MESH : Mice, Inbred C57BL, Biology, MESH : Interleukin-2, MESH: Receptors, Interleukin-2, MESH: Interphase, MESH: Lymphopenia, 03 medical and health sciences, Adjuvants, Immunologic, MESH: Mice, Inbred C57BL, MESH : Receptors, Interleukin-2, Lymphopenia, MESH : Mice, Animals, Lymphocyte Count, Antigen-presenting cell, Interphase, MESH: Mice, 030304 developmental biology, Interleukin 3, MESH : Bone Marrow Transplantation, Receptors, Interleukin-2, MESH: Interleukin-2, Survival Analysis, MESH : T-Lymphocyte Subsets, Mice, Inbred C57BL, MESH : Adjuvants, Immunologic, MESH : Mice, Knockout, Interleukin-2, MESH : Animals, MESH : Survival Analysis, 030215 immunology
Abstract

We show that the lymphoid hyperplasia observed in IL-2Rα- and IL-2-deficient mice is due to the lack of a population of regulatory cells essential for CD4 T cell homeostasis. In chimeras reconstituted with bone marrow cells from IL-2Rα-deficient donors, restitution of a population of CD25+CD4+ T cells prevents the chaotic accumulation of lymphoid cells, and rescues the mice from autoimmune disease and death. The reintroduction of IL-2-producing cells in IL-2-deficient chimeras establishes a population of CD25+CD4+ T cells, and restores the peripheral lymphoid compartments to normal. The CD25+CD4+ T cells regulated selectively the number of naive CD4+ T cells transferred into T cell-deficient hosts. The CD25+CD4+/naive CD4 T cell ratio and the sequence of cell transfer determines the homeostatic plateau of CD4+ T cells. Overall, our findings demonstrate that IL-2Rα is an absolute requirement for the development of the regulatory CD25+CD4+ T cells that control peripheral CD4 T cell homeostasis, while IL-2 is required for establishing a sizeable population of these cells in the peripheral pools.

Published
2002

7. Clonally diverse T cell homeostasis is maintained by a common program of cell-cycle control

Author

Daniel Commenges, Robin E. Callard, Andrew J. Yates, Thea Hogan, Benedict Seddon, A. N. Shuvaev, Rodolphe Thiébaut, Institute of Child Health [London], University College of London [London] (UCL), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Albert Einstein College of Medicine [New York], Division of Immune Cell Biology, Medical Research Council-Nationale Institute for Medical Research, Biotechnology and Biological Sciences Council, U.K., and the Agence Nationale de la Recherche, France., Thiébaut, Rodolphe, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Université Bordeaux Segalen - Bordeaux 2

Subjects
Adoptive cell transfer, Cell division, Cellular differentiation, Cell, MESH: Cell Cycle, MESH: T-Lymphocyte Subsets, Lymphocyte Activation, MESH: Mice, Knockout, Immune Regulation, Mice, 0302 clinical medicine, T-Lymphocyte Subsets, Homeostasis, Immunology and Allergy, MESH: Animals, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], Mice, Knockout, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Cell Cycle, Cell Differentiation, MESH: Receptors, Antigen, T-Cell, Cell cycle, Adoptive Transfer, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Cell biology, medicine.anatomical_structure, MESH: Homeostasis, MESH: Cell Division, Clone (B-cell biology), Cell Division, MESH: Cell Differentiation, MESH: Immunophenotyping, MESH: Mice, Transgenic, T cell, Immunology, Receptors, Antigen, T-Cell, Mice, Transgenic, Biology, MESH: Models, Immunological, Cell Line, Immunophenotyping, MESH: Lymphopenia, 03 medical and health sciences, MESH: Mice, Inbred C57BL, Lymphopenia, medicine, Animals, MESH: Lymphocyte Activation, MESH: Mice, 030304 developmental biology, T-cell receptor, MESH: Clone Cells, Models, Immunological, Clone Cells, MESH: Cell Line, Mice, Inbred C57BL, MESH: Adoptive Transfer, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], 030215 immunology
Abstract

Lymphopenia induces T cells to undergo cell divisions as part of a homeostatic response mechanism. The clonal response to lymphopenia is extremely diverse, and it is unknown whether this heterogeneity represents distinct mechanisms of cell-cycle control or whether a common mechanism can account for the diversity. We addressed this question by combining in vivo and mathematical modeling of lymphopenia-induced proliferation (LIP) of two distinct T cell clonotypes. OT-I T cells undergo rapid LIP accompanied by differentiation that superficially resembles Ag-induced proliferation, whereas F5 T cells divide slowly and remain naive. Both F5 and OT-I LIP responses were most accurately described by a single stochastic division model where the rate of cell division was exponentially decreased with increasing cell numbers. The model successfully identified key biological parameters of the response and accurately predicted the homeostatic set point of each clone. Significantly, the model was successful in predicting interclonal competition between OT-I and F5 T cells, consistent with competition for the same resource(s) required for homeostatic proliferation. Our results show that diverse and heterogenous clonal T cell responses can be accounted for by a single common model of homeostasis.

Published
2013

8. Imatinib sensitizes T-cell lymphocytes from chronic myeloid leukemia patients to FasL-induced cell death: a brief communication

Author

Emmanuelle Stebe, Philippe Rousselot, Delphine Rea, Jill Patrice Cassuto, Anne-Odile Hueber, Francois-Xavier Mahon, Laurence Legros, Nathalie Ebran, Institut de Biologie Valrose (IBV), 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)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Service d'Hématologie Clinique, Hôpital l'Archet, Transfert de Genes a Visee Therapeutique Dans les Cellules Souches, and Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, Cancer Research, Lymphocyte, MESH: Piperazines, Apoptosis, MESH: Flow Cytometry, Cell Separation, Lymphocyte Activation, Fas ligand, Piperazines, 0302 clinical medicine, MESH: Aged, 80 and over, hemic and lymphatic diseases, Immunology and Allergy, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Aged, 80 and over, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Myeloid leukemia, Middle Aged, Fas receptor, Flow Cytometry, 3. Good health, MESH: Antigens, CD95, Leukemia, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Benzamides, Imatinib Mesylate, Female, medicine.drug, Adult, Fas Ligand Protein, T cell, Immunology, Antineoplastic Agents, chemical and pharmacologic phenomena, Biology, MESH: Cell Separation, MESH: Lymphopenia, 03 medical and health sciences, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Lymphopenia, medicine, Humans, fas Receptor, MESH: Lymphocyte Activation, 030304 developmental biology, Aged, Pharmacology, MESH: Humans, MESH: Apoptosis, Imatinib, MESH: Adult, medicine.disease, MESH: Male, MESH: Fas Ligand Protein, Imatinib mesylate, Pyrimidines, MESH: Leukemia, Myelogenous, Chronic, BCR-ABL Positive, MESH: Pyrimidines, MESH: Antineoplastic Agents, MESH: Female
Abstract

International audience; There is now substantial evidence that imatinib may affect immune responses, especially those mediated by T lymphocytes. Fas (CD95/Apo-1), a cell death receptor, is a key regulator of the immune system. We have explored the consequences of treatment on the Fas system in chronic myeloid leukemia patients treated with imatinib. In comparison with healthy controls, we found not only a mild blood lymphopenia but also impairment of phytohemagglutinin activation in CD4Fas and CD8Fas lymphocytes of imatinib-treated patients. Moreover, these lymphocyte populations were more sensitive to FasL-induced cell death in relation to an increase in Fas expression at the cell surface. Taken together, these results reveal the role of Fas receptor in the lymphopenia observed in patients treated with imatinib, with potential deleterious consequences on antileukemic responses against this immunogenic hematological malignancy.

Published
2012

9. Effects of in vivo chronic hydrocarbons pollution on sanitary status and immune system in sea bass (Dicentrarchus labrax L.)

Author

Rami Kanan, Claire Quentel, Stéphane Le Floch, François Lamour, Morgane Danion, Laboratoire de Ploufragan - Plouzané, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Centre de documentation de recherche et d'expérimentations sur les pollutions accidentelles des eaux (Cedre), and Cedre

Subjects
Health Status, Health, Toxicology and Mutagenesis, MESH: Random Allocation, Bioconcentration, 010501 environmental sciences, MESH: Leukopenia, MESH: Phagocytes, 01 natural sciences, Leukocyte Count, Random Allocation, MESH: Body Burden, Blood plasma, Leukocytes, MESH: Animals, Polycyclic Aromatic Hydrocarbons, Toxicity Tests, Chronic, MESH: Health Status, media_common, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, Phagocytes, 0303 health sciences, biology, Petroleum, medicine.anatomical_structure, MESH: Water Pollutants, Chemical, Environmental chemistry, Body Burden, Dicentrarchus, MESH: Bass, MESH: Petroleum, Pollution, media_common.quotation_subject, Aquatic Science, Gas Chromatography-Mass Spectrometry, MESH: Leukocytes, MESH: Lymphopenia, 03 medical and health sciences, MESH: Polycyclic Hydrocarbons, Aromatic, Animal science, Immune system, Lymphopenia, White blood cell, medicine, Animals, 14. Life underwater, Sea bass, 030304 developmental biology, 0105 earth and related environmental sciences, Pollutant, MESH: Toxicity Tests, Chronic, Leukopenia, biology.organism_classification, MESH: Gas Chromatography-Mass Spectrometry, 13. Climate action, MESH: Leukocyte Count, Bass, Water Pollutants, Chemical
Abstract

International audience; Following the development of an experimental system to expose adult fish to low and stable concentration of pollutant over a prolonged period, the in vivo effects of hydrocarbons on sanitary status, i.e. the health status of fish with regard to chemical pollution, and immune system in sea bass, Dicentrarchus labrax were assessed. A total of 90 fish were acclimated for 15 days, then 45 fish were exposed to the water soluble fraction (WSF) of Arabian crude oil, similar to a complex pollution by hydrocarbons chronically observed in situ in estuaries, while the 45 other control fish sustained the same experimental conditions in clean seawater. After 21 days of exposure, 30 contaminated and control fish were sampled, then 30 other fish were collected after a 15 day recovery period in clean sea water. PAH concentrations in crude oil, WSF, muscles and bile were measured by gas chromatography coupled with mass spectrometry analysis. White blood cell counts and differential leucocyte counts were determined by classical haematology methods. Cell mortality and phagocytosis activity of leucocytes were analyzed by flow cytometry. Haemolytic alternative complement activity and stress parameters were analyzed in blood plasma by spectrophotometry. After a 21 day exposure period to a mixture of 41 parent/alkylated-PAHs (835 ± 52/85 ± 1 5 ng L(-1)). Fish flesh was contaminated by a bioconcentration of naphthalene very closed to the Reference Dose for Oral Exposure estimated by US-EPA's Integrated Risk Information System, causing a potential risk for human consumers. A leucopenia due to a lymphopenia, a rise in leucocyte mortality and a decrease in phagocytosis activity were noted in contaminated fish compared to controls. All these results may be explained by the damage to membrane cells integrity by uptake of PAHs and suggested an impairment of specific and nonspecific immune systems. After a 15 day recovery period, effects were reversible for sanitary status and an offset in immunity was noted by a significant increase in leucocytes in contaminated fish compared to controls.

Published
2011

10. Diagnosis and treatment of digestive cryptosporidiosis in allogeneic haematopoietic stem cell transplant recipients: a prospective single centre study

Author

E. Deconinck, Faezeh Legrand, Frédéric Grenouillet, Frédéric Dalle, Fabrice Larosa, Philippe Saas, Laurence Millon, Pierre Rohrlich, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Laboratoire Interactions Muqueuses Agents Transmissibles ( LIMA ), Université de Bourgogne ( UB ), 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]), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire Interactions Muqueuses Agents Transmissibles (LIMA), and Université de Bourgogne (UB)

Subjects
Male, medicine.medical_treatment, MESH : Cryptosporidium parvum, Cryptosporidiosis, Graft vs Host Disease, Hematopoietic stem cell transplantation, Azithromycin, Gastroenterology, 0302 clinical medicine, immune system diseases, MESH : Thiazoles, MESH: Animals, MESH : Female, 030212 general & internal medicine, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, MESH : Azithromycin, [ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Antibacterial agent, 0303 health sciences, MESH: Middle Aged, biology, MESH : Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, MESH: Immunosuppression, Nitazoxanide, Immunosuppression, Hematology, Middle Aged, MESH : Adult, Nitro Compounds, MESH : Diagnosis, Differential, 3. Good health, Cryptosporidium parvum, surgical procedures, operative, MESH: Young Adult, Female, medicine.symptom, MESH : Lymphopenia, medicine.drug, Adult, medicine.medical_specialty, MESH : Transplantation, Homologous, MESH : Male, MESH : Young Adult, MESH: Thiazoles, MESH: Graft vs Host Disease, Asymptomatic, MESH: Lymphopenia, Diagnosis, Differential, 03 medical and health sciences, Young Adult, MESH: Diagnosis, Differential, Internal medicine, MESH: Azithromycin, Lymphopenia, MESH : Hematopoietic Stem Cell Transplantation, medicine, MESH: Transplantation, Homologous, Animals, Humans, Transplantation, Homologous, MESH : Middle Aged, MESH : Cryptosporidiosis, MESH: Hematopoietic Stem Cell Transplantation, Immunosuppression Therapy, Transplantation, MESH: Humans, 030306 microbiology, business.industry, MESH: Cryptosporidiosis, MESH : Humans, MESH: Adult, biology.organism_classification, MESH: Male, Thiazoles, Immunology, MESH : Immunosuppression, MESH: Cryptosporidium parvum, MESH : Animals, business, MESH: Female
Abstract

International audience; Digestive cryptosporidiosis (DC) can mimic GVHD after allogeneic haematopoietic stem cell transplantation (HSCT), thus requiring a reduction of immunosuppressive drugs and a specific therapy, whereas GVHD requires an intensification of immunosuppression. We systematically searched for cryptosporidiosis by light microscopy, immunochromatography and PCR in HSCT recipients who presented with at least one episode of diarrhoea. Of 115 consecutive patients allografted between July 2006 and November 2008, we analysed stools in 52 of 56 patients meeting these criteria. We identified Cryptosporidium parvum in 5 of the 52 patients (9.6%) at a median of 503 days (range 20-790) after HSCT. In those five patients, the median CD4+ cell and B lymphocyte counts were 60/mm3 (0-234) and 0/mm3 (0-96), respectively. Two patients died of invasive fungal infections. In the other three patients, diarrhoea disappeared after a median of 5 weeks following onset of bitherapy with azithromycine and nitazoxanide; they were still alive 433, 380 and 1179 days after the DC diagnosis. DC is probably under diagnosed after HSCT because it is difficult to detect during the asymptomatic phase. Early bitherapy and reduction of immunosuppression seem efficacious. In our series, DC has a seasonal pattern and is promoted by profound T lymphopenia.

Published
2011

11. Enhanced T cell recovery in HIV-1-infected adults through IL-7 treatment

Author

Jean-François Delfraissy, Cécile Goujard, François Boué, Thérèse Croughs, Rodolphe Thiébaut, Christine Lacabaratz, Jean-Michel Molina, Yves Levy, Jean-Daniel Lelièvre, Stéphanie Beq, Véronique Avettand-Fenoel, Jean-Paul Viard, Geneviève Chêne, Christine Rouzioux, Laurence Weiss, Michel Morre, Service d'immunologie clinique [Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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), 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), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie antivirale systémique et cérébrale, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne et maladies infectieuses, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Immunologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Henri-Mondor Albert-Chenevier, Hôpital Antoine Béclère, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Service de maladies infectieuses et tropicales [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Cythéris, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), 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 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Paris-Sud - Paris 11 ( UP11 ) -IFR93-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Henri-Mondor Albert-Chenevier, Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Santé Publique, d'Epidémiologie et de Développement ( ISPED ), and Guellaen, Georges

Subjects
MESH: CD4 Lymphocyte Count, medicine.medical_treatment, T-Lymphocytes, Cell, MESH : Aged, MESH : Prospective Studies, CD4-CD8 Ratio, HIV Infections, MESH: Cell Cycle, Lymphocyte Activation, MESH: Recombinant Proteins, MESH: HIV-1, 0302 clinical medicine, Prospective Studies, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Cell Cycle, General Medicine, Drug Tolerance, MESH: HIV Infections, MESH : Adult, Cell cycle, Middle Aged, Recombinant Proteins, 3. Good health, medicine.anatomical_structure, MESH: Immunologic Memory, MESH : Lymphopenia, Safety, MESH : HIV-1, Research Article, MESH : Interleukin-7, Adult, MESH : Recombinant Proteins, MESH : Immunologic Memory, T cell, MESH: Drug Tolerance, MESH: Lymphopenia, 03 medical and health sciences, Antigen, Lymphopenia, MESH : Cell Cycle, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : CD4 Lymphocyte Count, MESH : HIV Infections, medicine, Humans, MESH : Middle Aged, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Safety, MESH: Lymphocyte Activation, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Lymphocyte Activation, 030304 developmental biology, Aged, MESH : T-Lymphocytes, MESH: Humans, business.industry, Interleukin-7, MESH : Humans, MESH: Safety, MESH: Adult, Immunotherapy, medicine.disease, T cell deficiency, MESH: Interleukin-7, MESH: Prospective Studies, CD4 Lymphocyte Count, MESH: T-Lymphocytes, MESH : CD4-CD8 Ratio, MESH : Drug Tolerance, Immunology, HIV-1, MESH: CD4-CD8 Ratio, business, Immunologic Memory, CD8, 030215 immunology
Abstract

International audience; HIV infection results in CD4+ T cell deficiency, but efficient combination antiretroviral therapy (c-ART) restores T cells and decreases morbidity and mortality. However, immune restoration by c-ART remains variable, and prolonged T cell deficiency remains in a substantial proportion of patients. In a prospective open-label phase I/IIa trial, we evaluated the safety and efficacy of administration of the T cell regulator IL-7. The trial included 13 c-ART-treated HIV-infected patients whose CD4+ cell counts were between 100 and 400 cells/microl and plasma HIV RNA levels were less than 50 copies/ml. Patients received a total of 8 subcutaneous injections of 2 different doses of recombinant human IL-7 (rhIL-7; 3 or 10 microg/kg) 3 times per week over a 16-day period. rhIL-7 was well tolerated and induced a sustained increase of naive and central memory CD4+ and CD8+ T cells. In the highest dose group, 4 patients experienced transient increases in viral replication. However, functional assays showed that the expanded T cells responded to HIV antigen by producing IFN-gamma and/or IL-2. In conclusion, in lymphopenic HIV-infected patients, rhIL-7 therapy induced substantial functional and quantitative changes in T cells for 48 weeks. Therefore, patients may benefit from intermittent therapy with IL-7 in combination with c-ART.

Published
2009

12. Lymphocyte subsets in renal transplant recipients with de novo genitourinary malignancies

Author

J M Rebibou, Dominique Simula-Faivre, Philippe Saas, Hugues Bittard, Didier Ducloux, Jean Marc Chalopin, G. Guichard, Pierre Tiberghien, François Kleinclauss, Service d'urologie, andrologie et transplantation rénale, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, 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]), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), 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)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Plateforme de Biomonitoring, Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Néphrologie et Urologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Centre d'Investigation Clinique de Besançon ( CICB ), Etablissement Français du Sang Bourgogne Franche-Comté-Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Franche-Comté ( UFC ), Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ), 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 ), Saas, Philippe, Hôpital Saint-Jacques-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), 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), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), and Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC)

Subjects
CD4-Positive T-Lymphocytes, Male, MESH : Retrospective Studies, medicine.medical_treatment, MESH : Aged, 030232 urology & nephrology, MESH: T-Lymphocyte Subsets, 030230 surgery, Gastroenterology, MESH: Kidney Transplantation, MESH : Carcinoma, Renal Cell, 0302 clinical medicine, T-Lymphocyte Subsets, Renal cell carcinoma, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, Kidney transplantation, MESH: Aged, education.field_of_study, MESH: Middle Aged, Incidence (epidemiology), MESH: CD4-Positive T-Lymphocytes, MESH: Carcinoma, Renal Cell, Middle Aged, Kidney Neoplasms, 3. Good health, MESH: Urinary Bladder Neoplasms, MESH : Urinary Bladder Neoplasms, MESH : CD4-Positive T-Lymphocytes, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Lymphopenia, MESH : Prostatic Neoplasms, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Male, Urology, Population, MESH: Lymphopenia, 03 medical and health sciences, Lymphopenia, Internal medicine, medicine, Humans, MESH : Middle Aged, education, Carcinoma, Renal Cell, Dialysis, Aged, Retrospective Studies, MESH: Humans, business.industry, Genitourinary system, MESH : Humans, Prostatic Neoplasms, MESH: Retrospective Studies, medicine.disease, Kidney Transplantation, MESH : T-Lymphocyte Subsets, MESH : Kidney Neoplasms, MESH: Male, Urinary Bladder Neoplasms, MESH: Prostatic Neoplasms, Immunology, MESH : Kidney Transplantation, Skin cancer, Lymphocytopenia, MESH: Kidney Neoplasms, business, MESH: Female
Abstract

Introduction: The incidence of genitourinary tumors (GUT) in renal transplant recipients (RTR) is higher than in the general population. We previously reported that CD4 lymphocytopenia is associated with a high incidence of skin cancer in RTR. Here, we investigate whether persistent CD4 T cell lymphopenia is associated with GUT occurrence. Patients and Methods: A total of 433 patients were included in this study. All patients underwent annually systematic lymphocyte subset (CD3, CD4, CD8, CD19) determination by flow cytometry. Results and Conclusion: During the follow-up period, 13 patients developed GUT: 6 patients a prostate adenocarcinoma (incidence 0.06%/year) and 7 patients a renal cell carcinoma (incidence 0.07%/year). The patients with GUT were older than those without. Both groups did not differ in posttransplant duration, dialysis mode and duration, induction regimen, or acute rejection history. No persistent CD4 lymphopenia was observed in the patients with GUT. Although CD4 T cell lymphopenia is associated with skin cancer in long-term RTR, it did not appear to be a risk factor for GUT. This suggests that other factors encountered in the setting of kidney transplantation (e.g., immunosuppressive drugs, end-stage renal failure, etc.) favor the development of GUT in RTR.

Published
2008

13. 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

14. 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

15. Familial NK cell deficiency associated with impaired IL-2- and IL-15-dependent survival of lymphocytes

Author

Jean-Jacques Mention, Jean-Laurent Casanova, Emmanuelle Jouanguy, Laure Gineau, Alexandre Alcaïs, Jean-Claude Carel, Anne Puel, Celine Eidenschenk, Françoise Le Deist, Eric Vivier, Benoit Pasquier, Ingrid M. Fleckenstein, Haon, Marie Laure, Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), 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 ), Immunologie, génétique et traitement des maladies métaboliques et du diabète ( UMR_S 561 ), 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 ), Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-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), Immunologie, génétique et traitement des maladies métaboliques et du diabète (UMR_S 561), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)

Subjects
Lymphocyte, MESH : Lymphocytes, MESH: Interleukin-15, Apoptosis, MESH : Child, Preschool, Interleukin 21, MESH : Child, MESH: Child, Immunology and Allergy, Cytotoxic T cell, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, IL-2 receptor, Lymphocytes, Child, Interleukin-15, MESH : Cell Survival, MESH : Infant, MESH: Infant, MESH: Case-Control Studies, Killer Cells, Natural, medicine.anatomical_structure, MESH: Cell Survival, Interleukin 15, Child, Preschool, Interleukin 12, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Killer Cells, Natural, MESH : Lymphopenia, MESH: Killer Cells, Natural, MESH : Case-Control Studies, MESH: Immunologic Deficiency Syndromes, Adolescent, [SDV.IMM] Life Sciences [q-bio]/Immunology, Cell Survival, T cell, Immunology, MESH : Interleukin-15, Biology, MESH : Family Health, MESH : Interleukin-2, MESH: Lymphopenia, MESH : Adolescent, Lymphopenia, medicine, Humans, MESH: Adolescent, Family Health, MESH: Humans, MESH: Apoptosis, MESH: Child, Preschool, MESH : Humans, Immunologic Deficiency Syndromes, Infant, MESH: Interleukin-2, MESH : Immunologic Deficiency Syndromes, Case-Control Studies, MESH: Family Health, Interleukin-2, MESH: Lymphocytes, MESH: Female, CD8, MESH : Apoptosis
Abstract

We previously reported the clinical phenotype of two siblings with a novel inherited developmental and immunodeficiency syndrome consisting of severe intrauterine growth retardation and the impaired development of specific lymphoid lineages, including transient CD8 αβ T lymphopenia and a persistent lack of blood NK cells. We describe here the elucidation of a plausible underlying pathogenic mechanism, with a cellular phenotype of impaired survival of both fresh and herpesvirus saimiri-transformed T cells, in the surviving child. Clearly, NK cells could not be studied. However, peripheral blood T lymphocytes displayed excessive apoptosis ex vivo. Moreover, the survival rates of CD4 and CD8 αβ T cell blasts generated in vitro, and herpesvirus saimiri-transformed T cells cultured in vitro, were low, but not nil, following treatment with IL-2 and IL-15. In contrast, Fas-mediated activation-induced cell death was not enhanced, indicating a selective excess of cytokine deprivation-mediated apoptosis. In keeping with the known roles of IL-2 and IL-15 in the development of NK and CD8 T cells in the mouse model, these data suggest that an impaired, but not abolished, survival response to IL-2 and IL-15 accounts for the persistent lack of NK cells and the transient CD8 αβ T lymphopenia documented in vivo. Impaired cytokine-mediated lymphocyte survival is likely to be the pathogenic mechanism underlying this novel form of inherited and selective NK deficiency in humans.

Published
2006

16. Different competitive capacities of Stat4- and Stat6-deficient CD4+ T cells during lymphophenia-driven proliferation

Author

Vanesa Sanchez-Guajardo, José A. M. Borghans, Maria-Elena Marquez, Sylvie Garcia, Antonio A. Freitas, Biologie des Populations Lymphocytaires, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Immunologie Moléculaire, and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
CD4-Positive T-Lymphocytes, Time Factors, MESH: Lymph Nodes, Lymphocyte Activation, MESH: Down-Regulation, Mice, 0302 clinical medicine, immune system diseases, Homeostasis, Immunology and Allergy, MESH: Animals, Phosphorylation, skin and connective tissue diseases, MESH: Bone Marrow Transplantation, STAT4, Bone Marrow Transplantation, STAT6, Mice, Knockout, Mice, Inbred BALB C, 0303 health sciences, integumentary system, Effector, MESH: CD4-Positive T-Lymphocytes, STAT4 Transcription Factor, respiratory system, Adoptive Transfer, Cell biology, DNA-Binding Proteins, medicine.anatomical_structure, MESH: Homeostasis, MESH: Cell Division, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cell activation, Cell Division, T cell, Immunology, MESH: Mice, Inbred BALB C, Down-Regulation, Biology, MESH: Lymphopenia, 03 medical and health sciences, Immune system, Lymphopenia, MESH: Cell Proliferation, parasitic diseases, medicine, Animals, MESH: Lymphocyte Activation, MESH: Mice, Cell Proliferation, 030304 developmental biology, Th1 Cells, MESH: Adoptive Transfer, Trans-Activators, Lymph Nodes, Bone marrow, STAT6 Transcription Factor, MESH: DNA-Binding Proteins, 030215 immunology
Abstract

The outcome of an immune response relies on the competitive capacities acquired through differentiation of CD4+ T cells into Th1 or Th2 effector cells. Because Stat4 and Stat6 proteins are implicated in the Th1 vs Th2 generation and maintenance, respectively, we compare in this study the kinetics of Stat4−/− and Stat6−/− CD4+ T cells during competitive bone marrow reconstitution and lymphopenia-driven proliferation. After bone marrow transplantation, both populations reconstitute the peripheral T cell pools equally well. After transfer into lymphopenic hosts, wild-type and Stat6−/− CD4+ T cells show a proliferation advantage, which is early associated with the expression of an active phospho-Stat4 and the down-regulation of Stat6. Despite these differences, Stat4- and Stat6-deficient T cells reach similar steady state numbers. However, when both Stat4−/− and Stat6−/− CD4+ T cells are coinjected into the same hosts, the Stat6−/− cells become dominant and out-compete Stat4−/− cells. These findings suggest that cell activation, through the Stat4 pathway and the down-regulation of Stat6, confers to pro-Th1 T cells a slight proliferation advantage that in a competitive situation has major late repercussions, because it modifies the final homeostatic equilibrium of the populations and favors the establishment of Th1 CD4+ T cell dominance.

Published
2005

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