期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 41, 期 1, 页码 60-66出版社
WILEY-BLACKWELL
DOI: 10.1002/eji.201040873
关键词
B lymphocyte-induced maturation protein 1; IL-2; IL-15 receptor alpha; T-box expressed in T cells
类别
资金
- School of Clinical Medicine, University of Cambridge
- Agency for Science, Technology & Research (A*STAR)
- Wellcome Trust
The T-box transcription factor, T-bet promotes the differentiation of short-lived effector CD8(+) T cells at the expense of central memory cells. How T-bet mediates these effects, and whether they are directly caused by T-bet alone are unknown, because expression of T-bet requires stimulation of the T cell by inflammatory and growth cytokines, which may have T-bet-independent functions involving T-cell differentiation. We developed an in vitro system of ectopic T-bet expression that avoids the effects of inflammatory cytokines to determine which aspects of the T-bet phenotype may be accounted for by T-bet alone. Ectopic T-bet expression by OT-I CD8(+) T cells stimulated by the H2-Kb (SIINFEKL) complex and cultured with 2 ng/mL IL-2 induced a coordinated change in gene expression leading to down-regulation of CD127 and SOCS-1 and up-regulation of CD122 and IL-15 receptor alpha, switching the cellular survival cytokine from IL-7 to IL-15. T-bet expression and 2 ng/mL IL-2 also led to a capacity for IFN-gamma and Fas ligand expression, confirming a role in eliciting these effector functions. Finally, ectopic T-bet promoted the expression of B lymphocyte-induced maturation protein 1 by OT-I cells in the presence of 20 ng/mL IL-2, providing a mechanism for the role of T-bet in driving terminal differentiation in concert with a high level of IL-2 receptor signalling.
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