CD4highCD8low double-positive T cells with high differentiation mediate incomplete immune reconstitution in HIV-infected patients

Abstract

Abstract Antiretroviral therapy (ART) is the most generally used to treat human immunodeficiency virus (HIV)-infected patients. However, some patients experience incomplete immune reconstitution and fail to restore CD4+ T cell counts after treating with ART. Herein, we investigated the characters of CD4+CD8+ double-positive (DP) T cells at the transcriptomic level by analyzing single-cell RNA sequencing of peripheral blood mononuclear cells from HIV-infected immunological non-responders (INRs) and immunological responders (IRs). We identified eight DP T cell clusters and grouped into three populations CD4highCD8low, CD4lowCD8high, and CD4lowCD8low, respectively. Decreased proportion of DP T cells was detected in INRs, including CD4highCD8low DP T cells in the process of cellular differentiation, the latter demonstrated a reduced source of DP T cells in INRs. CD4highCD8low DP T cells in IRs and INRs as a heterogenous population, were distinct on the expression of GZMA/B/H, LAG3, NKG7 and GNLY, which related to the function of cell activation and cellular differentiation, cytotoxicity and programmed cell death. These data provide a comprehensive analysis of gene signatures of CD4highCD8low DP T cells associated with failed immune reconstitution after HIV infection, which could be useful in developing new cure strategies for HIV-infected patients.