The transcription factor IRF4 is essential for TCR affinity-mediated metabolic programming and clonal expansion of T cells
journal contribution
posted on 2023-05-20, 04:44authored byMan, K, Miasari, M, Shi, W, Xin, A, Darren HenstridgeDarren Henstridge, Preston, S, Pellegrini, M, Belz, GT, Smyth, GK, Febbraio, MA, Nutt, SL, Kallies, A
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.