Elevation of Tim-3 and PD-1 Expression on T Cells Appears Early in HIV Infection, and Differential Tim-3 and PD-1 Expression Patterns Can Be Induced by Commonγ-Chain Cytokines

摘要

Purpose. To explore the association between differential Tim-3 and PD-1 expression patterns and HIV disease progression, and to investigate the impact of commonγ-chain cytokines on Tim-3 and PD-1 expression patterns on T cells.Methods. Tim-3/PD-1 expression on the T cells of patients with early and chronic HIV infections was detected. The expression levels and functional profiles of T cells with differential Tim-3 and PD-1 expression patterns induced byγ-chain cytokines were studied.Results. The elevation of differential Tim-3 and PD-1 expression patterns on T cells appeared early in HIV infection. Co-expression of Tim-3 and PD-1 (Tim-3+PD-1+) correlates with more severe exhaustion of T cells during HIV infection. In vitro stimulation of commonγ-chain cytokines can induce differential expression patterns of Tim-3 and PD-1 on T cells. The enhancement of Tim-3 and PD-1 expression by commonγ-chain IL-2 can inhibit the function of T cells re-stimulated by HIV gag and TCR, not by the re-stimulation of IL-2.Conclusions. The elevation of differential Tim-3 and PD-1 expression patterns on T cells represents a state of T cell exhaustion and can be induced by commonγ-chain cytokines. These findings provide insights into HIV pathogenesis and help inform immune intervention strategies.