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NFATc2 and NFATc3 regulate TH2 differentiation and modulate TCR-responsiveness of naïve TH cells

Nature Immunology volume 3, pages 48–54 (2002)Cite this article

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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Figure 1: Naïve THp cells from DKO mice intrinsically differentiate into TH2-type cells but retain the capacity for TH1 polarization.
Figure 2: TH2 differentiation is not dependent on IL-4 production by TKO mice.
Figure 3: DKO and TKO THp cells show increased proliferation in response to stimulation.
Figure 4: Proliferation of naïve DKO and TKO cells upon engagement of TCR alone or both TCR and CD28.
Figure 5: Analysis of naïve THp cell division in response to TCR and CD28 ligation.
Figure 6: Intrinsic TH2 differentiation in DKO TH cells requires only TCR engagement in vitro.

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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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Authors and Affiliations

  1. Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Ave., FXB-2, Boston, 02115-6017, MA, USA

    Jyothi Rengarajan, Betty Tang & Laurie H. Glimcher

  2. Department of Medicine, Harvard Medical School, Boston, 02115, MA, USA

    Laurie H. Glimcher

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  1. Jyothi Rengarajan
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  2. Betty Tang
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Correspondence to Laurie H. Glimcher.

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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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