Published in

Nature Research, Nature Immunology, 11(14), p. 1155-1165, 2013

DOI: 10.1038/ni.2710

Nature Research, Nature Immunology, 9(15), p. 894-894, 2014

DOI: 10.1038/ni0914-894b

Links

Tools

Export citation

Search in Google Scholar

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

Journal article published in 2013 by Kevin Man, Maria Miasari, Wei Shi, Annie Xin, Darren C. Henstridge, Simon Preston, Marc Pellegrini ORCID, Gabrielle T. Belz, Gordon K. Smyth, Mark A. Febbraio ORCID, Stephen L. Nutt ORCID, Axel Kallies
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

Full text: Download

Green circle
Preprint: archiving allowed
Upload
Orange circle
Postprint: archiving restricted
Upload
Red circle
Published version: archiving forbidden
Policy details
Data provided by SHERPA/RoMEO

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.