Journal article
A molecular threshold for effector CD8 T cell differentiation controlled by transcription factors Blimp-1 and T-bet
A Xin, F Masson, Y Liao, S Preston, T Guan, R Gloury, M Olshansky, JX Lin, P Li, TP Speed, GK Smyth, M Ernst, WJ Leonard, M Pellegrini, SM Kaech, SL Nutt, W Shi, GT Belz, A Kallies
Nature Immunology | NATURE PUBLISHING GROUP | Published : 2016
DOI: 10.1038/ni.3410
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 da..
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Awarded by National Institutes of Health
Funding Acknowledgements
We thank M. Camilleri and L. Mackiewicz for technical support, and M. Ghisi (Peter MacCallum Cancer Centre) for assistance with MetaCore bioinformatics analysis. Supported by the National Health and Medical Research Council of Australia (program grant 1054618 to T.P.S. and G.K.S.; fellowship 1058892 to G.K.S.; project grant 1023454 to G.K.S. and W.S.; project grant 637345 to A.K. and G.T.B.; project grant 1042582 to G.T.B. and M.P.; project grant 603122 to M.E.), the Sylvia and Charles Viertel Foundation (A.K. and G.T.B.), the Australian Research Council (S.L.N., G.T.B. and A.K.), the US National Institutes of Health (NIH) (R01AI066232 and R0O1AI074699 to S.M.K.), the Howard Hughes Medical Institute (S.M.K.), the Howard Hughes Medical Institute International Student Fellowship (T.G.), the Division of Intramural Research and the DNA Sequencing Core, National Heart, Lung, and Blood Institute, NIH (W.J.L.), the Adam J. Berry Memorial Fund, jointly provided by the Australian Academy of Science and NIH (A.X.) and the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institute Infrastructure Support scheme.