系统性红斑狼疮患者T细胞TCR/CD3复合物介导的信号传导研究

Disorder of TCR/CD3 complex-mediated signal transduction in T cells from patients with SLE

目的 :证实SLE患者T细胞功能异常是否与其生物化学信号转导异常有关。方法 :用CD3单抗与羊抗鼠二抗IgG相交联刺激T细胞并用Thapsigargin和EGTA干预后 ,分别用粘附细胞仪连续观察 1 0minT细胞 [Ca2 +]i的变化 ,并评价[Ca2 +]i反应与CD3分子和InsP3 生成量的相关性。结果 :正常人和SLE患者T细胞 [Ca2 +]i反应的基准值相似 (P =0 1 0 5) ;SLE患者T细胞的 [Ca2 +]i反应高峰值、平台值明显高于正常对照 (P <0 0 0 1 ,P <0 0 0 1 ) ;加入Thapsigargin后二者 [Ca2 +]i反应无显著差异 ,而加入EGTA后二者 [Ca2 +]i反应有显著差异 ;二者的T细胞CD3阳性率和InsP3 生成量无差异 (P =0 665 ,P =0 537)。结论 :SLE患者T细胞TCR CD3介导的信号转导途径存在异常 ;SLE患者T细胞功能异常可能是因细胞内生物化学信号途径异常所致。

Objective:To investigate whether SLE T cells fuction the of is relative to abnormal signal transduction pathways.Methods:After cross linking of anti CD3 mAbs to sheep anti mouse Ig and stimulating T cells,the changes of free calcium biochemicalion within T cells and these changes under interference of Thapsigargin and EGTA was observed respectively successively for 10 minutes by an adhesion cytometry.The relation between [Ca 2+ ]i responses in SLE T cells and expression of CD3 molecular,or InsP 3 levels was evaluated.Results:The base [Ca 2+ ]i response in T cells from SLE patients was similar to that from normal control ( P =0 105),peak and plateau [Ca 2+ ]i responses were significantly higher in the group of SLE patients ( P <0.001, P <0.001),[Ca 2+ ]i responses were similar in both individuals after addition of Thapsigargin,[Ca 2+ ]i responses of T cells from SLE patients in the presence of EGTA were higher,the percentage of the CD3 + cells and InsP 3 generation were similar in both individuals ( P =0.665, P =0.537).Conclusion:TCR/CD3 mediated [Ca 2+ ]i responses in T cells from SLE patients was abnormal,and T cell function disorder in SLE mayresult from the by product of abnormal biochemical pathways.