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

Annie Xin, Frederick Masson, Yang Liao, Simon Peter Preston, Tianxia Guan, Renee Gloury, Moshe Olshansky, Jian Xin Lin, Peng-Peng Li, Terence P Speed, Gordon K Smyth, Matthias Ernst, Warren J. Leonard, Marc Pellegrini, Susan M. Kaech, Stephen L Nutt, Wei Shi, Gabrielle T Belz, Axel Kallies

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83 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)422-432
Number of pages11
JournalNature Immunology
Volume17
Issue number4
DOIs
Publication statusPublished - 1 Apr 2016
Externally publishedYes

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