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A molecular threshold for effector CD8+ T cell differentiation controlled by transcription factors Blimp-1 and T-bet
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A molecular threshold for effector CD8+ T cell differentiation controlled by transcription factors Blimp-1 and T-bet
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Journal Article
A molecular threshold for effector CD8+ T cell differentiation controlled by transcription factors Blimp-1 and T-bet
2016
Overview
Using genetic approaches and transcriptional profiling, Kallies and colleagues reveal a common program of effector CD8
+
T cell differentiation that is regulated by the cooperation of IL-2 and IL-12 signaling and the combined activities of the transcriptional regulators Blimp-1 and T-bet.
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
Nature Publishing Group US,Nature Publishing Group
Subject
/ 45
/ 45/91
/ 64/60
/ Animals
/ Arenaviridae Infections - immunology
/ CD8-Positive T-Lymphocytes - immunology
/ Cell Differentiation - immunology
/ Chromatin Immunoprecipitation
/ Influenza A Virus, H1N1 Subtype
/ Lymphocytic choriomeningitis virus
/ Mice
/ Orthomyxoviridae Infections - immunology
/ Positive Regulatory Domain I-Binding Factor 1
/ Real-Time Polymerase Chain Reaction
/ STAT4 Transcription Factor - immunology
/ STAT5 Transcription Factor - immunology
