期刊
CYTOKINE
卷 57, 期 1, 页码 191-199出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.cyto.2011.10.006
关键词
Cytokines; CD8 T cell; Signal transduction; Knock out mice
资金
- National Institutes of Health [AI050699]
CD8+ T cell synthesis of IFN-gamma is an important component of the CD8+ T cell immune response. In short-term cultures of murine pan-T cells, we found that IL-4 was the principal cytokine responsible for driving IFN-gamma synthesis by CD3/CD28-activated CD8+ T cells. IL-4 was able to induce low levels of IFN-gamma mRNA in CD8+ T cells even in the absence of CD3/CD28 engagement, although concomitant CD3/CD28 stimulation was necessary for IFN-gamma secretion. IL-4 induction of IFN-gamma was explained by its ability to induce Eomesodermin and T-bet transcription factors whose expression was further increased by CD3/CD28. Expression of Eomesodermin, T-bet and IFN-gamma induced by IL-4 was partially dependent upon activation of MAPK and PI3K but independent of the canonical IL-4-activated transcription factor, STAT6. In contrast, expression of IFN-gamma induced by IL-4/CD3/CD28 stimulation showed additional dependency upon STAT6 which functions to increase expression of Eomesodermin specifically. These novel findings point to a function for IL-4 as a direct regulator of IFN-gamma expression in CD8+ T cells and reveal the molecular mechanisms involved. (C) 2011 Elsevier Ltd. All rights reserved.
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