Cytotoxic CD8+T cells expressing CXCR5 are detectable in HIV-1 elite controllers after prolonged in vitro peptide stimulation
Autor: | Philipp Adams, Gilles Iserentant, Jean-Yves Servais, Linos Vandekerckhove, Guido Vanham, Carole Seguin-Devaux, the PhenoCure Study Group |
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Přispěvatelé: | PhenoCure Study Group, Faculty of Medicine and Pharmacy, Pathologic Biochemistry and Physiology, Clinical sciences, Internal Medicine |
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Adult
Male lcsh:Immunologic diseases. Allergy 0301 basic medicine T cell Immunology HIV Infections/drug therapy Gene Expression Regulation/drug effects Receptors CXCR5/immunology Stimulation Biology CD8-Positive T-Lymphocytes/immunology elite controllers CXCR5 03 medical and health sciences HIV-1/immunology viral suppressive capacity Medicine and Health Sciences medicine Humans Immunology and Allergy Cytotoxic T cell functional cure Secretion Aged ELISPOT HIV controllers CXCR5 CD8 T cells + + Middle Aged 030112 virology In vitro 030104 developmental biology medicine.anatomical_structure Peptides/immunology multifunctional CD8(+) T cells CXCR5 CD8 T cells + plus multifunctional CD8+ T cells Female Human medicine lcsh:RC581-607 Immunologic Memory CD8 |
Zdroj: | Frontiers in immunology FRONTIERS IN IMMUNOLOGY Frontiers in Immunology, Vol 11 (2021) |
ISSN: | 1664-3224 |
Popis: | Antiretroviral therapy (ART) is not curative as HIV-1 persists in long-lived viral reservoirs. Consequently, patients are dependent on life-long drug adherence with possible side effects. To overcome these limitations strategies of a functional cure aim at ART free viral remission. In this study, we sought to identify detailed subsets of anti-viral CD8+ T cell immunity linked to natural long-term control of HIV-1 infection. Here, we analyzed HIV controllers and ART suppressed progressors for in vitro viral suppressive capacity (VSC) at baseline and after peptide stimulation. Functional properties and phenotypes of CD8+ T cells were assessed by IFN-γ ELISPOT and 18 color flow cytometry. HIV controllers showed significantly increased suppression at baseline as well as after peptide stimulation. IFN-γ secretion and the proliferation marker Ki67 positively correlated with VSC. Moreover, the detailed phenotype of three distinct multifunctional memory CD8+ T cell subsets were specific traits of HIV controllers of which two correlated convincingly with VSC. Our results underline the importance of multifunctional CD8+ T cell responses during natural control. Especially the role of CXCR5 expressing cytotoxic subsets emphasizes potential surveillance in sites of reservoir persistence and demand further study. |
Databáze: | OpenAIRE |
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