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Gene regulation mediated by calcium signals in T lymphocytes

Nature Immunology volume 2, pages 316–324 (2001)Cite this article

A Corrigendum to this article was published on 01 March 2008

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Abstract

Modulation of many signaling pathways in antigen-stimulated T and B cells results in global changes in gene expression. Here we investigate the contribution of calcium signaling to gene expression in T cells using cell lines from two severe-combined immunodeficiency patients with several cytokine deficiencies and diminished activation of the transcription factor NFAT nuclear factor of activated T cells. These T cells show a strong defect in transmembrane calcium influx that is also apparent in their B cells and fibroblasts. DNA microarray analysis of calcium entry–deficient and control T cells shows that Ca2+ signals both activate and repress gene expression and are largely transduced through the phosphatase calcineurin. We demonstrate an elaborate network of signaling pathways downstream of the T cell receptor, explaining the complexity of changes in gene expression during T cell activation.

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Figure 1: Dephosphorylation and nuclear translocation of NFAT in SCID patients' T cells is facilitated by high [Ca2+]ex.
Figure 2: The SCID patients' T cells have a primary defect in transmembrane calcium influx.
Figure 3: The calcium entry defect affects SCID patients' B cells and fibroblasts.
Figure 4: Calcium-dependent gene expression in T cells.
Figure 5: T cells deficient in calcium influx fail to repress the expression of certain genes.
Figure 6: Calcineurin is involved in expression of most of calcium-regulated genes.
Figure 7: Calcineurin is involved in expression of most calcium-regulated genes.

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Change history

  • 06 February 2008

    In the version of the article initially published, many errors and inappropriate manipulations were made in Figures 1, 3 and 5 (see PDF for details).

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Acknowledgements

We thank C. Niemeyer for providing us with the patient data. Supported in part by grants from the Deutsche Forschungsgemeinschaft (Fe496/1-1) and in part by NIH grants CA42471 and AI40127.

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Authors and Affiliations

  1. Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, 02115, MA, USA

    Stefan Feske & Anjana Rao

  2. Division of Clinical Sciences, Metabolism Branch, National Cancer Institute, Bethesda, 20892, MD, USA

    Jena Giltnane & Louis M. Staudt

  3. Children's Hospital, Harvard Medical School, Boston, 02115, MA, USA

    Ricardo Dolmetsch

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Correspondence to Anjana Rao.

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Feske, S., Giltnane, J., Dolmetsch, R. et al. Gene regulation mediated by calcium signals in T lymphocytes. Nat Immunol 2, 316–324 (2001). https://doi.org/10.1038/86318

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