Journal
NATURE IMMUNOLOGY
Volume 2, Issue 4, Pages 316-324Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/86318
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Funding
- NCI NIH HHS [CA42471] Funding Source: Medline
- NIAID NIH HHS [AI40127] Funding Source: Medline
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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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