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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism*
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CD4-Positive T-Lymphocytes / virology
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism*
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CD8-Positive T-Lymphocytes / virology
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Cell Differentiation
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Cell Proliferation
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Clone Cells
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Gene Expression Regulation
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Humans
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Influenza A Virus, H3N2 Subtype / immunology
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Interferon Regulatory Factors / genetics
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Interferon Regulatory Factors / immunology
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Interferon Regulatory Factors / metabolism*
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Mice
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Mice, Transgenic
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Orthomyxoviridae Infections / immunology
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Orthomyxoviridae Infections / metabolism*
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Orthomyxoviridae Infections / virology
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / immunology
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Receptors, Antigen, T-Cell / metabolism*
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism*
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T-Lymphocyte Subsets / virology
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Transcription, Genetic
Substances
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Interferon Regulatory Factors
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Receptors, Antigen, T-Cell
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interferon regulatory factor-4
Associated data
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GEO/GSE49929
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GEO/GSE49930
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GEO/GSE49931