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IL‐27 induction of IL‐21 from human CD8 + T cells induces granzyme B in an autocrine manner
Author(s) -
Mittal Akanksha,
Murugaiyan Gopal,
Bey Vanessa,
Hu Dan,
Weiner Howard L
Publication year - 2012
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2012.14
Subject(s) - granzyme b , cytotoxic t cell , granzyme , autocrine signalling , interleukin 21 , cd8 , biology , interleukin 15 , interleukin 12 , il 2 receptor , microbiology and biotechnology , interleukin 3 , t cell , chemistry , immune system , perforin , immunology , cell culture , in vitro , biochemistry , genetics
Interleukin (IL)‐27 exerts an anti‐inflammatory effect on human and mice CD4 + T cells by inducing IL‐10‐producing T regulatory 1 cells through induction of IL‐21. However, the role of IL‐27 and how it regulates IL‐21 from human CD8 + T cells is unclear. Here, we show that the IL‐27 receptor is expressed on human CD8 + T cells and stimulation of human naïve CD8 + T cells in the presence of IL‐27 leads to an increase in IL‐21 and interferon (IFN)‐γ production. IL‐21 induction in IL‐27‐stimulated human CD8 + T cells correlates specifically with expression of the transcription factor T‐bet. IL‐27 stimulation of naïve CD8 + T cells induces a double‐positive T‐bet + IL‐21 + expressing CD8 + T‐cell population. Furthermore, IL‐27 stimulation of human naïve CD8 + T cells greatly increases expression of granzyme B. Antibody‐mediated neutralization of IL‐21 abrogates IL‐27‐induced granzyme B expression. Moreover, direct addition of IL‐21 greatly amplifies granzyme B expression in human naïve CD8 + T cells. Our findings identify IL‐27‐induced IL‐21 as a key autocrine regulator of granzyme B expression in human CD8 + T cells.