Abstract
GATA-3 controls T helper type 2 (TH2) differentiation. However, whether GATA-3 regulates the function of mature T cells beyond TH2 determination remains poorly understood. We found that signaling via the T cell antigen receptor (TCR) and cytokine stimulation promoted GATA-3 expression in CD8+ T cells, which controlled cell proliferation. Although GATA-3-deficient CD8+ T cells were generated, their peripheral maintenance was impaired, with lower expression of the receptor for interleukin 7 (IL-7R). GATA-3-deficient T cells had defective responses to viral infection and alloantigen. The proto-oncoprotein c-Myc was a critical target of GATA-3 in promoting T cell proliferation. Our study thus demonstrates an essential role for GATA-3 in controlling the maintenance and proliferation of T cells and provides insight into immunoregulation.
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Acknowledgements
We thank M. Busslinger and A. Souabni (Research Institute of Molecular Pathology) for Gata3fl/fl mice; N. Fisher and J. Kalnitsky for cell sorting; and M. Su for discussions. Supported by the US National Institutes of Health (R01AI097392), National Multiple Sclerosis Society (RG4654) and the University Cancer Research Fund (Y.Y.W.).
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Y.W. designed and did cellular, molecular and biochemical experiments; Y.W., I.M. and J.K.W. did LCMV-infection experiments and contributed to the writing of the manuscript; A.-D.G. contributed to the graft-versus-host response experiments; T.A.C. and L.S. provided critical genetic models and intellectual inputs; and Y.Y.W. designed experiments, wrote the manuscript and provided overall direction.
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Wang, Y., Misumi, I., Gu, AD. et al. GATA-3 controls the maintenance and proliferation of T cells downstream of TCR and cytokine signaling. Nat Immunol 14, 714–722 (2013). https://doi.org/10.1038/ni.2623
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DOI: https://doi.org/10.1038/ni.2623
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