A molecular threshold for effector CD8(+) T cell differentiation controlled by transcription factors Blimp-1 and T-bet
- Author(s)
- Xin, A; Masson, F; Liao, Y; Preston, S; Guan, T; Gloury, R; Olshansky, M; Lin, JX; Li, P; Speed, TP; Smyth, GK; Ernst, M; Leonard, WJ; Pellegrini, M; Kaech, SM; Nutt, SL; Shi, W; Belz, GT; Kallies, A;
- Details
- Publication Year 2016-04,Volume 17,Issue #4,Page 422-32
- Journal Title
- Nat Immunol
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- NPG
- Research Division(s)
- Molecular Immunology; Infection And Immunity; Bioinformatics
- PubMed ID
- 26950239
- Publisher's Version
- https://doi.org/10.1038/ni.3410
- NHMRC Grants
- NHMRC/1054618, NHMRC/1058892, NHMRC/1023454, NHMRC/637345, NHMRC/1042582,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2016-03-15 03:47:49
Last Modified: 2016-08-19 10:24:59