Abstract

Antigen-stimulated T and B cells show modulation of many signaling pathways, resulting in global changes in gene expression. Here we investigate the contribution of Ca2+ signaling to gene expression in T cells, using cell lines from two severe combined immunodeficiency (SCID) patients with multiple cytokine deficiencies and diminished activation of the transcription factor NFAT. T cells from the patients show a strong defect in transmembrane calcium influx (CI), that is also apparent in their B cells and fibroblasts. DNA microarray analysis of calcium entry-deficient and control T cells illustrates that Ca2+ signals both activate and repress gene expression and are largely transduced through the phosphatase calcineurin. This analysis reveals an unexpectedly elaborate network of signaling pathways downstream of the TCR, explaining the complexity of changes in gene expression during T cell activation.