CD4⁺ T Memory Stem Cells Correlate with Disease Progression in Chronically HIV-1-Infected Patients

Recently identified T memory stem (Tscm) cells have stem-cell-like properties, including long lifespan, self-renewal capacity, and multipotency to differentiate into other memory T cell types. In the study of simian immunodeficiency virus (SIV) infection, selective depletion of CCR5⁺CD4⁺ Tscm cells and the high proliferation rate of these cells are believed to be responsible for the pathogenesis of SIV-infected rhesus macaques. Here, we conducted a cohort study to investigate the influence of chronic human immunodeficiency virus (HIV)-1 infection on CD4⁺ Tscm cell homeostasis, and the effect of antiretroviral therapy (ART) on CD4⁺ Tscm cells. Chronic HIV-1 infection resulted in a decrease of the CD4⁺ Tscm cell proportion in HIV-1 patients. The decreased number of CD4⁺ Tscm cells in HIV-1 patients correlated positively with that of circulating CD4⁺ T cells. Further, the depletion of CD4⁺ Tscm cells was inversely correlated with an increased level of T cell immune activation during chronic HIV-1 infection. Prolonged ART recovered the CD4⁺ Tscm cells, and the dynamic change of CD4⁺ Tscm cells was in parallel with CD4⁺ T cell restoration and a decrease in the level of T cell immune activation. We propose that the abnormity of CD4⁺ Tscm cells may contribute to the pathogenesis and disease progression in HIV-1-infected individuals.