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The transcription factor IRF4 is essential for TCR affinity-mediated metabolic programming and clonal expansion of T cells

Citation

Man, K and Miasari, M and Shi, W and Xin, A and Henstridge, DC and Preston, S and Pellegrini, M and Belz, GT and Smyth, GK and Febbraio, MA and Nutt, SL and Kallies, A, The transcription factor IRF4 is essential for TCR affinity-mediated metabolic programming and clonal expansion of T cells, Nature Immunology, 14, (11) pp. 1155-1165. ISSN 1529-2908 (2013) [Refereed Article]

Copyright Statement

Copyright 2013 Springer Nature

DOI: doi:10.1038/ni.2710

Abstract

During immune responses, T cells are subject to clonal competition, which leads to the predominant expansion of high-affinity clones; however, there is little understanding of how this process is controlled. We found here that the transcription factor IRF4 was induced in a manner dependent on affinity for the T cell antigen receptor (TCR) and acted as a dose-dependent regulator of the metabolic function of activated T cells. IRF4 regulated the expression of key molecules required for the aerobic glycolysis of effector T cells and was essential for the clonal expansion and maintenance of effector function of antigen-specific CD8+ T cells. Thus, IRF4 is an indispensable molecular 'rheostat' that 'translates' TCR affinity into the appropriate transcriptional programs that link metabolic function with the clonal selection and effector differentiation of T cells.

Item Details

Item Type:Refereed Article
Keywords:beta actin, CD8 antigen, Hermes antigen, interferon regulatory factor 4, interleukin 2 receptor alpha, T lymphocyte receptor, animal cell, antigen specificity, article, binding affinity, CD8+ T lymphocyte, cell expansion, cell metabolism, glycolysis
Research Division:Biological Sciences
Research Group:Biochemistry and Cell Biology
Research Field:Signal Transduction
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Immune System and Allergy
UTAS Author:Henstridge, DC (Mr Darren Henstridge)
ID Code:133345
Year Published:2013
Web of Science® Times Cited:172
Deposited By:Health Sciences
Deposited On:2019-06-24
Last Modified:2019-07-23
Downloads:0

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