Increased frequency of Foxp3+CD8+ T cells are associated with disease progression during HIV infection

Recent years have witnessed unprecedented strides in comprehending non-CD4 regulatory T cells (Tregs), such as CD8+ Tregs and double negative T cells (DNT cells), and their role in sustaining immune tolerance and restricting immune activation. This study investigates the role of Foxp3+CD8+ T cells during HIV infection and assess the markers associated with CD4+ Tregs. This study was designed as a cross-sectional cohort study, comprising 21 age-matched healthy controls (HCs), 122 treatment-naïve participants (TNs), and 60 people living with HIV (PLWH) receiving successful treatment (ARTs). The frequency of Foxp3+CD8+ T cells was assessed alongside CD4+ Treg-associated markers and plasma inflammatory factor levels. Foxp3+CD8+ T cells were enriched in PLWH with CD4+ T cell count < 350 cells/μl and persisted after antiretroviral therapy (ART). Besides, the Foxp3+CD8+T cells were correlated with CD4+ T cell count, CD4/CD8 ratio, and the parameters of activation and systematic inflammation in PLWH. Moreover, Foxp3+CD8+ T cells expressed different levels of Tregs related markers compared to CD4+ Tregs and Foxp3+ DNT cells. The Foxp3+CD8+T cells are associated with HIV disease progression and employ distinct mechanisms to exert their functions.