Abstract
The NFAT family of transcription factors are key regulators of inducible gene expression in the immune system. We examined the function of two NFAT proteins after naïve T helper (TH) cell activation. We found that naïve TH precursors that are doubly deficient in NFATc2 and NFATc3 intrinsically differentiate into TH2-secreting cells, even in the absence of interleukin 4 (IL-4) production. We also found that lack of NFATc2 and NFATc3 obviates the necessity for engagement of CD28 on naïve cells and controls the time required to reach the first cell division upon activation. These results demonstrate a key role for NFATc2 and NFATc3 in modulating T cell receptor responsiveness and regulating subsequent cell division and TH2 differentiation.
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Acknowledgements
We thank A. Wurster, S. Szabo and other members of the laboratory for discussions and comments on the manuscript; M. Handly and R. McGilp for FACS expertise; and C. McCall for preparing the manuscript. Supported by the National Institutes of Health AI31541-05 (L. H. G.), the G. Harold and Leila Y. Mathers Charitable Foundation (L. H. G.) and Fogarty International (J. R.).
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Rengarajan, J., Tang, B. & Glimcher, L. NFATc2 and NFATc3 regulate TH2 differentiation and modulate TCR-responsiveness of naïve TH cells. Nat Immunol 3, 48–54 (2002). https://doi.org/10.1038/ni744
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DOI: https://doi.org/10.1038/ni744
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