Gene regulation mediated by calcium signals in T lymphocytes

Modulation of many signaling pathways in antigen-stimulated T and B cells r esults in global changes in gene expression. Here we investigate the contri bution of calcium signaling to gene expression in T cells using cell lines from two severe-combined immunodeficiency patients with several cytokine de ficiencies and diminished activation of the transcription factor NFAT nucle ar factor of activated T cells. These T cells show a strong defect in trans membrane calcium influx that is also apparent in their B cells and fibrobla sts. 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 e laborate network of signaling pathways downstream of the T cell receptor, e xplaining the complexity of changes in gene expression during T cell activa tion.