title: IL-27 induction of IL-21 from human CD8+ T cells induces granzyme B in an autocrine manner.
abstract: 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.
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Akanksha
authors.initials: A
authors.lastname: Mittal
authors.forename: Gopal
authors.initials: G
authors.lastname: Murugaiyan
authors.forename: Vanessa
authors.initials: V
authors.lastname: Beynon
authors.forename: Dan
authors.initials: D
authors.lastname: Hu
authors.forename: Howard L
authors.initials: HL
authors.lastname: Weiner
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D049109:Cell Proliferation; D004790:Enzyme Induction / Q000276:immunology; D053804:Granzymes / Q000096:biosynthesis*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism* / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D000098546:Interleukin-21
chemical_list: C573415:IFNG protein, human; D007378:Interleukins; C464565:MYDGF protein, human; D007371:Interferon-gamma; C509213:GZMB protein, human; D053804:Granzymes; D000098546:Interleukin-21