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

R Schneider, T Yaneva, D Beauseigle… - European journal of …, 2011 - Wiley Online Library
R Schneider, T Yaneva, D Beauseigle, L El‐Khoury, N Arbour
European journal of immunology, 2011Wiley Online Library
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 …
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.
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