Alteration of CCR6+ CD95+ CD4+ naive T cells in HIV-1 infected patients: Implication for clinical practice

The profound deficiency of Th17 cells contributes to HIV disease progression. The mechanisms of their perturbation remain unclear. Recently, CCR6(+) CD95(+) CD4(+) naive T cells (CCR6(+) CD95(+) CD4(+) T-NA), identified as pre-committed Th17 precursors, were recognized as a subpopulation of CD4(+) T cells with stem cell properties. Following phenotypical identification, we evaluated their level in patients during chronic HIV infection and following antiretroviral therapy (ART) using flow cytometry. The levels of CCR6(+) CD95(+) CD4(+) T-NA were decreased during chronic HIV infection and correlated with CD4(+) T cell counts. Immunological responders harbored higher frequency of CCR6(+) CD95(+) CD4(+) T-NA, which was associated with CD4/CD8 T cell ratio. Immunological non-responders with lower frequency of CCR6(+) CD95(+) CD4(+) T-NA failed to exhibit a correlation between CCR6(+) CD95(+) CD4(+) T-NA and CCR6(+) CD95(+) CD4(+) T-CM, and displayed elevated ratio of CCR6(+) CD95(+) CD4(+) T-CM/T-NA. The number of CCR6(+) CD95(+) CD4(+) T-NA was increased following early ART. These findings shed light on the importance of targeting pre-committed Th17 precursors that enhance immune reconstitution.