Abstract
Antigen and cytokine receptor signals act in synergy to direct the differentiation of CD4+ T cells. These signals initiate reciprocal activation and silencing of the interferon-γ (IFN-γ) and interleukin 4 (IL-4) cytokine gene loci, changes that are heritably maintained in the resulting T helper type 1 (TH1) or TH2 cells and their progeny. Early, unpolarized transcription and chromatin remodeling of the poised cytokine genes of naive T cells is followed by consolidation and spreading of epigenetic changes and the establishment of self-reinforcing transcription factor networks. Recent studies have begun to elucidate the molecular mechanisms that establish and maintain polarized cytokine gene expression, and thus the cellular identity of differentiated helper T cells.
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Acknowledgements
We thank our colleagues for discussions. M.A. is supported by the Damon Runyon Cancer Research Fund (DRG-1682).
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Ansel, K., Lee, D. & Rao, A. An epigenetic view of helper T cell differentiation. Nat Immunol 4, 616–623 (2003). https://doi.org/10.1038/ni0703-616
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DOI: https://doi.org/10.1038/ni0703-616
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