Journal
FRONTIERS IN IMMUNOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2020.622343
Keywords
HIV controllers; functional cure; viral suppressive capacity; multifunctional CD8(+) T cells; CXCR5 CD8 T cells + plus; elite controllers
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Funding
- FNR in Luxembourg [PHD-2015-1-10111126]
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This study reveals that HIV controllers show significantly increased suppression at baseline and after peptide stimulation, indicating a positive correlation between IFN-gamma secretion, Ki67 proliferation marker, and viral suppressive capacity (VSC). Furthermore, detailed phenotypes of three distinct multifunctional memory CD8(+) T cell subsets are specific traits of HIV controllers, two of which are convincingly correlated with VSC. Our results underline the importance of multifunctional CD8(+) T cell responses during natural control.
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-gamma ELISPOT and 18 color flow cytometry. HIV controllers showed significantly increased suppression at baseline as well as after peptide stimulation. IFN-gamma 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.
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