Antigen sensitivity is a major determinant of CD8+ T-cell polyfunctionality and HIV-suppressive activity
| Autor: | Victor Appay, Jorge R. Almeida, Brigitte Autran, Daniel C. Douek, Gianfranco Pancino, Arnaud Moris, David Price, So Youn Shin, Martin Larsen, Delphine Sauce, Asier Sáez-Cirión, Laura Papagno |
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| Přispěvatelé: | CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Cardiff University, Régulation des Infections Rétrovirales, Institut Pasteur [Paris], Virus et Immunité, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Inserm AVENIR grant, the French ANRS, Sidaction, the National Institutes of Health, and the Medical Research Council (MRC) of the United Kingdom. D.A.P. is a MRC Senior Clinical Fellow. J.R.A. is supported by a fellowship from the Fundação para a Ciência e Tecnologia. S.Y.S. is supported by Korea Science and Engineering Foundation and the Institut Pasteur Korea., We are very grateful to the staff and patients who participated in this study and to the ANRS Cohort ALT group. Martha Nason provided invaluable help with statistical analysis. We thank Catherine Blanc for her skills in infected live cell sorting in the Pitié-Salpêtrière Flow Cytometry Platform. We are also indebted to Nathalie Rufer for the provision of rhIL-2., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cytotoxicity Immunologic HIV Antigens [SDV]Life Sciences [q-bio] clone cells HIV Infections hiv MESH: Flow Cytometry CD8-Positive T-Lymphocytes Virus Replication MESH: Clone Cells/immunology Biochemistry MESH: CD8-Positive T-Lymphocytes/immunology Epitopes 0302 clinical medicine antigens Cytotoxic T cell Immunity Cellular 0303 health sciences biology virus diseases Hematology Flow Cytometry 3. Good health medicine.anatomical_structure Lentivirus [SDV.IMM]Life Sciences [q-bio]/Immunology MESH: HIV-1/immunology MESH: Dose-Response Relationship Immunologic MESH: Epitopes T cell Immunology Dose-Response Relationship Immunologic MESH: Immunity Cellular MESH: CD4-Positive T-Lymphocytes/immunology MESH: Coculture Techniques 03 medical and health sciences Immune system Antigen In vivo medicine Humans MESH: Cytotoxicity Immunologic t-lymphocytes Immunobiology 030304 developmental biology MESH: Humans MESH: HIV-1/physiology MESH: Virus Replication Cell Biology biology.organism_classification Coculture Techniques MESH: HIV Antigens/immunology HIV-1 MESH: HIV Infections/immunology CD8 Ex vivo 030215 immunology |
| Zdroj: | Blood Blood, American Society of Hematology, 2009, 113 (25), pp.6351-6360. ⟨10.1182/blood-2009-02-206557⟩ ResearcherID Blood, 2009, 113 (25), pp.6351-6360. ⟨10.1182/blood-2009-02-206557⟩ |
| ISSN: | 0006-4971 1528-0020 |
| DOI: | 10.1182/blood-2009-02-206557⟩ |
| Popis: | CD8+ T cells are major players in the immune response against HIV. However, recent failures in the development of T cell–based vaccines against HIV-1 have emphasized the need to reassess our basic knowledge of T cell–mediated efficacy. CD8+ T cells from HIV-1–infected patients with slow disease progression exhibit potent polyfunctionality and HIV-suppressive activity, yet the factors that unify these properties are incompletely understood. We performed a detailed study of the interplay between T-cell functional attributes using a bank of HIV-specific CD8+ T-cell clones isolated in vitro; this approach enabled us to overcome inherent difficulties related to the in vivo heterogeneity of T-cell populations and address the underlying determinants that synthesize the qualities required for antiviral efficacy. Conclusions were supported by ex vivo analysis of HIV-specific CD8+ T cells from infected donors. We report that attributes of CD8+ T-cell efficacy against HIV are linked at the level of antigen sensitivity. Highly sensitive CD8+ T cells display polyfunctional profiles and potent HIV-suppressive activity. These data provide new insights into the mechanisms underlying CD8+ T-cell efficacy against HIV, and indicate that vaccine strategies should focus on the induction of HIV-specific T cells with high levels of antigen sensitivity to elicit potent antiviral efficacy. |
| Databáze: | OpenAIRE |
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