IL-27 increases the proliferation and effector functions of human naïve CD8+ T lymphocytes and promotes their development into Tc1 cells

Abstract

IL-27 has been shown to exhibit both pro- and anti-inflammatory properties; it favors mouse naïve CD4(+) T-cell differentiation into Th1 cells to the detriment of Th17 and Th2 skewing and regulates IL-10 and IL-17 production by human CD4(+) T cells. Moreover, IL-27 promotes proliferation and cytotoxic functions of mouse CD8(+) T lymphocytes, but no data are available on human CD8(+) T cells. We investigated the impact of IL-27 on human CD8(+) T cells. In contrast to mouse T cells, the IL-27 receptor (IL-27R), composed of T cell cytokine receptor (TCCR) and gp130, was detected on a greater percentage of human CD8(+) than CD4(+) T cells and these proportions increased upon polyclonal activation. IL-27 induced rapid STAT1 and STAT3 signaling, enhanced STAT1 protein levels, and induced SOCS1 and SOCS3 expression in a STAT1-dependent manner by human CD8(+) T cells. Addition of IL-27 to α-CD3-activated naïve CD8(+) T cells significantly increased T-box transcription factor expression levels, cell proliferation, and IFN-γ and granzyme B production leading to increased CD8(+) T-cell-mediated cytotoxicity. These results demonstrate that IL-27, a rapidly produced cytokine by activated APC, has a profound impact on human naïve CD8(+) T cells, driving them to become highly efficient Tc1 cells.