Cytotoxic CD8+T Cells Expressing CXCR5 Are Detectable in HIV-1 Elite Controllers After Prolonged In Vitro Peptide Stimulation

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.

Automated summary

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.