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GATA-3 controls the maintenance and proliferation of T cells downstream of TCR and cytokine signaling

Nature Immunology volume 14, pages 714–722 (2013)Cite this article

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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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Figure 1: GATA-3 expression in CD8+ T cells.
Figure 2: CD8+ T cell development in the absence of GATA-3.
Figure 3: Defective peripheral maintenance of GATA-3-deficient CD8+ T cells.
Figure 4: The function of activated CD8+ T cells requires GATA-3.
Figure 5: GATA-3 is important for the population expansion of activated CD8+ T cells in vivo.
Figure 6: GATA-3 controls c-Myc expression.

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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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Authors and Affiliations

  1. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

    Yunqi Wang, Ai-Di Gu, T Anthony Curtis, Lishan Su & Yisong Y Wan

  2. Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

    Yunqi Wang, Ichiro Misumi, Ai-Di Gu, T Anthony Curtis, Lishan Su, Jason K Whitmire & Yisong Y Wan

  3. Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

    Ichiro Misumi & Jason K Whitmire

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Contributions

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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Correspondence to Yisong Y Wan.

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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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