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

Kevin Man, Maria Miasari, Wei Shi, Annie Xin, Darren C. Henstridge, Simon Peter Preston, Marc Pellegrini, Gabrielle T Belz, Gordon K Smyth, Mark A Febbraio, Stephen L Nutt, Axel Kallies

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197 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1155-1165
Number of pages11
JournalNature Immunology
Volume14
Issue number11
DOIs
Publication statusPublished - 2013
Externally publishedYes

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