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

Stem cell-like memory T cells (T_SCM) 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 T_SCM. T_SCM 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⁺T_SCM was positively correlated with the reduced frequency of T-bet⁺ in T cells. An increased mean fluorescence intensity of TOX was observed in CD4⁺T_SCM from PLWH. The frequency of T progenitor exhausted-like cells (T_PEX) within CD8⁺T cells was positively associated with the frequency of GZMK⁺cells in CD4⁺T_SCM. In addition, the frequency of stem-like T cells (T_STEM) in CD4⁺T cells was positively correlated with the frequency of T-bet⁺cells in CD4⁺T_SCM. T_SCM from virally suppressed PLWH exihibt impaired stemness and multipotency, potentially contributing to poor immune reconstitution.