Format

Send to

Choose Destination
Nat Immunol. 2016 Apr;17(4):422-32. doi: 10.1038/ni.3410. Epub 2016 Mar 7.

A molecular threshold for effector CD8(+) T cell differentiation controlled by transcription factors Blimp-1 and T-bet.

Author information

1
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
2
The Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
3
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
4
The Department of Computing and Information Systems, University of Melbourne, Parkville, Victoria, Australia.
5
Laboratory of Molecular Immunology and Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
6
The Department of Mathematics and Statistics, University of Melbourne, Parkville, Victoria, Australia.
7
Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.

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.

PMID:
26950239
PMCID:
PMC5779087
DOI:
10.1038/ni.3410
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center