Analysis reveals CXCR5+ T cells in elite controllers show enhanced immune responses, emphasizing viral control mechanisms.
Description Early ART preserves immune function and associates with post-treatment control of HIV. Yet, differences in immune responses among people with HIV (PWH) who initiated ART during acute vs. chronic infection and how these responses differ from elite controllers (ECs)–who control HIV without ART, remain poorly defined. Using 40-parameter CyTOF, we analyzed total and HIV-specific T cells from PWH enrolled in the UCSF SCOPE cohort, who began ART during acute (n = 16) or chronic (n = 10) infection and ECs (n = 10). PBMCs collected pre-ART and post-ART were assessed at baseline and after 6-hour stimulation with HIV peptides. HIV-specific T cells were defined by their induction of any combination of 12 effector cytokine/cytolytic markers upon stimulation. Pre-ART, total CD4+ T cell frequencies were higher in acute-treated PWH than chronic-treated PWH and ECs (P < 0.0005) and there was no significant change in these frequencies post-ART. Pre-ART, total CD4+ and CD8+ T cells in ECs expressed higher CXCR5 (P < 0.05 for both cell types) than their counterparts from the other groups. HIV-specific CD8+ T cells from ECs also showed higher CXCR5 (P < 0.0005) expression than cells from the other groups. These findings suggest that while both chronic-treated PWH and ECs show CD4+ T cell depletion, total and HIV-specific T cells from ECs show high levels of CXCR5, which may help direct these immune cells to lymphoid follicles, a primary site of HIV persistence, where they may help mediate viral control. Funding Sources Supported by NIH P01 AI69606; NIH 5T32AI007334-34 (Molecular and Cellular Immunology, UCSF); NIH 5T32HD007263-39 (Integrated Training in Reproductive Sciences, UCSF) Topic Categories Viral Immunology (VIR)
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