The role of soluble IL-7 receptor α in murine CD8+ T-cell responses (105.22)

Abstract

Abstract The expression of membrane-bound IL-7 receptor α (CD127) is reduced in many viral infections. In HIV infection, this downregulation may be explained in part by increased plasma levels of a soluble form of CD127 (sCD127). We and others have shown that the activity of human IL-7 and cytotoxic CD8+T-cell (CTL) function is decreased by sCD127 in vitro. Observed impairment of IL-7 activity in HIV infection may contribute to the decline of CTL function. The role of sCD127 in such immunopathogenesis is not known. Determining the role of sCD127-mediated immune modulation necessitates the use of an in vivo model. The effect of sCD127 on the IL-7 response of murine splenic CD8+T-cells was evaluated. CFSE-labeled naïve CD8+T-cells were incubated with medium, IL-7 or pre-complexed IL-7 + sCD127 and cell proliferation was assessed. Unlike human T-cells, the survival of murine T-cells in vitro is dependent on the addition of γ-chain receptor cytokines to the culture medium. Cells cultured with sCD127 + IL-7 were less viable and proliferated less (as measured by cell division) compared to IL-7 alone. Our results indicate that sCD127 inhibits the activity of IL-7 on murine naïve CD8+T-cells in vitro, confirming previous results in human T-cell culture. These data suggest that the biological activity of sCD127 on CD8+T-cells is similar between mice and humans, thus providing rationale for the further study of sCD127 in established murine models of CD8+T-cell-mediated responses to infection.