期刊
NATURE IMMUNOLOGY
卷 17, 期 4, 页码 422-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3410
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资金
- National Health and Medical Research Council of Australia [1054618, 1058892, 1023454, 637345, 1042582, 603122]
- Sylvia and Charles Viertel Foundation
- Australian Research Council
- US National Institutes of Health (NIH) [R01AI066232, R0O1AI074699]
- Howard Hughes Medical Institute
- Howard Hughes Medical Institute International Student Fellowship
- Division of Intramural Research
- DNA Sequencing Core, National Heart, Lung, and Blood Institute, NIH
- Australian Academy of Science
- NIH
- Victorian State Government Operational Infrastructure Support
- Australian Government NHMRC Independent Research Institute Infrastructure Support scheme
T cell responses are guided by cytokines that induce transcriptional regulators, which ultimately control differentiation of effector and memory T cells. However, it is unknown how the activities of these molecular regulators are coordinated and integrated during the differentiation process. Using genetic approaches and transcriptional profiling of antigen-specific CD8(+) T cells, we reveal a common program of effector differentiation that is regulated by IL-2 and IL-12 signaling and the combined activities of the transcriptional regulators Blimp-1 and T-bet. The loss of both T-bet and Blimp-1 leads to abrogated cytotoxic function and ectopic IL-17 production in CD8(+) T cells. Overall, our data reveal two major overlapping pathways of effector differentiation governed by the availability of Blimp-1 and T-bet and suggest a model for cytokine-induced transcriptional changes that combine, quantitatively and qualitatively, to promote robust effector CD8(+) T cell differentiation.
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