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

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

来源：Nature Immunology, 2016, 17(4): 422-+.

DOI：10.1038/ni.3410

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.

• 出版日期2016-4
• 单位河北医科大学