Feske S, Giltnane J, Dolmetsch R, Staudt L M, Rao A
Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Nat Immunol. 2001 Apr;2(4):316-24. doi: 10.1038/86318.
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.
抗原刺激的T细胞和B细胞中许多信号通路的调节会导致基因表达的全局性变化。在这里，我们使用来自两名患有多种细胞因子缺陷且活化T细胞核因子（NFAT）转录因子激活减弱的重症联合免疫缺陷患者的细胞系，研究钙信号对T细胞基因表达的作用。这些T细胞在跨膜钙内流方面表现出严重缺陷，这在它们的B细胞和成纤维细胞中也很明显。对钙内流缺陷型和对照T细胞进行DNA微阵列分析表明，Ca2+信号既能激活也能抑制基因表达，并且主要通过磷酸酶钙调神经磷酸酶进行转导。我们证明了T细胞受体下游存在一个复杂的信号通路网络，这解释了T细胞激活过程中基因表达变化的复杂性。
