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Start Over Author "Lio Collias" Topic immune activation
2 results on '"Lio Collias"'

1. Potential Role of Vδ2+ γδ T Cells in Regulation of Immune Activation in Primary HIV Infection

Author

Nupur Bhatnagar, Pierre-Marie Girard, Moises Lopez-Gonzalez, Céline Didier, Lio Collias, Corinne Jung, Diane Bollens, Claudine Duvivier, Cassandre Von Platen, Daniel Scott-Algara, Laurence Weiss, for the ANRS EP-56 Group, Nadia Valin, Laurent Fonquernie, Marina Karmochkine, Philippe Castiel, Anne Dumont, and Lucie Marchand

Subjects
primary HIV infection, Vδ2+ γδ T cells, immune activation, TGF-β, chronic HIV infection, Immunologic diseases. Allergy, RC581-607
Abstract

Although conventional regulatory T cells (Tregs) are sufficient in controlling low residual T-cell activation in ART-treated patients, they are not efficient in controlling exaggerated immune activation associated with high levels of HIV replication in primary HIV infection (PHI). Our previous data suggested that double negative (DN) T cells including mainly γδ DN T cells play a role in the control of immune activation in PHI. Since γδ T cells are capable of exerting regulatory functions, we investigated their implication as Tregs in PHI as well as chronic HIV infection (CHI). In a cross-sectional study of 58 HIV-infected patients, in the primary and the chronic phase either ART-treated or untreated (UT), we analyzed phenotype and cytokine production of γδ T cells using flow cytometry. Cytokine production was assessed following in vitro stimulation with isopentenyl pyrophosphate or plate-bound anti-CD3/anti-CD28 monoclonal antibodies. We found that the proportion of γδ T cells negatively correlated with CD8 T-cell activation in PHI patients. Furthermore, we found that in these patients, the Vδ2 receptor bearing (Vδ2+) γδ T cells were strongly activated, exhibited low terminal differentiation, and produced the anti-inflammatory cytokine, TGF-β. In contrast, in UT-CHI, we observed a remarkable expansion of γδ T cells, where the Vδ2+ γδ T cells comprised of an elevated proportion of terminally differentiated cells producing high levels of IFN-γ but very low levels of TGF-β. We also found that this loss of regulatory feature of γδ T cells in CHI was a lasting impairment as we did not find recovery of TGF-β production even in ART-CHI patients successfully treated for more than 5 years. Our data therefore suggest that during the primary HIV infection, Vδ2+ γδ T cells may act as Tregs controlling immune activation through production of TGF-β. However, in CHI, γδ T cells transform from an anti-inflammatory into pro-inflammatory cytokine profile and participate in sustenance of immune activation.

Published
2017
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2. γδ T-cell subsets in HIV controllers

Author

Mathieu F. Chevalier, Pierre-Marie Girard, Claudine Duvivier, Moises Lopez-Gonzalez, Lio Collias, Céline Didier, Corinne Jung, Diane Bollens, Juliette Pavie, Laurence Weiss, Daniel Scott-Algara, Nupur Bhatnagar, Régulation des Infections Rétrovirales, Institut Pasteur [Paris], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Cytokines et Inflammation, 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 Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'infectiologie Necker-Pasteur [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)-Institut Pasteur [Paris], Université Sorbonne Paris Cité (USPC), This study was supported by the Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (ANRS). M.F.C and N.B received a grant from the ANRS., We thank all patients who participated in this study. We also thank Rita Affa who provided support for on-site project implementation, and management of ethical and regulatory clearance under the supervision of Nathalie Jolly (CRT Clinical Core, Institut Pasteur, Paris). We thank the Pasteur Institute (Paris) for promoting the study, and Françoise Barré-Sinoussi and Jean-Marc Cavaillon for their scientific support., ANRS-EP56 Group included Nadia Valin and Laurent Fonquernie, Hôpital Saint Antoine, Paris, Marina Karmochkine, and Philippe Castiel, Hôpital Européen Georges Pompidou, Paris, Véronique Avettand-Fénoël, Hôpital Necker-Enfants malades, Paris. Anne Dumont and Lucie Marchand, Service des recherches cliniques sur les hépatites virales et le VIH, ANRS INSERM, Paris, France., Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Adult, Male, 0301 basic medicine, endocrine system, T cell, T gd 17, Immunology, Human immunodeficiency virus (HIV), HIV Infections, Viremia, medicine.disease_cause, immune activation, HIV Long-Term Survivors, interleukin-17, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, transforming growth factor- b, Antigen, T-Lymphocyte Subsets, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Immunology and Allergy, Medicine, Cytotoxic T cell, 030212 general & internal medicine, Receptor, chronic HIV infection, medicine.diagnostic_test, business.industry, HIV controllers, virus diseases, Receptors, Antigen, T-Cell, gamma-delta, Middle Aged, Flow Cytometry, medicine.disease, 3. Good health, 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, Cytokines, Female, gd T cells, business
Abstract

International audience; OBJECTIVES:HIV controllers (HICs) are rare HIV-infected individuals able to maintain undetectable viremia in the absence of antiretroviral treatment. Although HIV-specific cytotoxic T cells have been well deciphered in HIC, γδ T lymphocytes remain largely uncharacterized. The aim of this study was to analyse phenotypic and functional characteristics of γδ T cells and their relationship with immune activation, which remains abnormally elevated and associated with comorbidities in HICs.METHODS:Peripheral blood mononuclear cells (PBMCs) were isolated from 16 HICs, 16 patients with untreated chronic HIV infection (UT-CHI) and 20 healthy donors. Surface marker expression and cytokine production by γδ T cells were analysed by flow cytometry.RESULTS:Despite normal frequencies of total γδ T cells, the Vδ2/Vδ2 ratio was significantly reduced in HIC, albeit to a lesser extent than UT-CHI patients. Of note, nine HICs showed elevated Vδ2 γδ T cells, as patients with UT-CHI, which was associated with higher CD8 T-cell activation. Interleukin (IL)-17-production by γδ T cells (Tγδ17) was better preserved in HIC than in UT-CHI patients. Proportion of total γδ T cells positively correlated with CD8 T-cell activation and HIV-DNA, IP-10 and sCD14 levels. Conversely, Tγδ17 cells negatively correlated with CD8 T-cell activation and plasma sCD14 levels. Moreover, transforming growth factor (TGF)-β producing Vδ2 T cells were as dramatically depleted in HIC as in UT-CHI patients.CONCLUSION:The relative preservation of IL-17-producing γδ T cells in HIC and their negative association with immune activation raise the hypothesis that Tγδ17 cells - potentially through prevention of microbial translocation - may participate in the control of chronic systemic immune activation.

Published
2019
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