Residual Exhaustion of Stem Cell-Like Memory T Cells (TSCM) in HIV Infected Patients With Viral Suppression.

Stem cell-like memory T cells (TSCM) play a pivotal role at the top of the memory T cell hierarchy, understanding their involvement in immune exhaustion during HIV infection may shed light on T cell dysfunction mechanisms. We compared cellular immunity between virally suppressed people living with HIV (PLWH) under antiretroviral therapy (ART) and HIV-negative subjects. Flow cytometry was used to assess the phenotype and function of peripheral TSCM. TSCM showed a reduction in the expression level of TCF-1, T-bet, as well as in multifunctional capacity, which was reflected by decreased secretion of IL-2+TNF-a+INF-γ+cells in PLWH. The decreased frequencies of IL-2+TNF-a+INF-γ+TSCM was positively correlated with the reduced frequency of T-bet+ in T cells. An increased mean fluorescence intensity of TOX was observed in CD4+TSCM from PLWH. The frequency of T progenitor exhausted-like cells (TPEX) within CD8+T cells was positively associated with the frequency of GZMK+cells in CD4+TSCM. In addition, the frequency of stem-like T cells (TSTEM) in CD4+T cells was positively correlated with the frequency of T-bet+cells in CD4+TSCM. TSCM from virally suppressed PLWH exihibt impaired stemness and multipotency, potentially contributing to poor immune reconstitution.