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

TCR/CD3 complex-mediated signal transduction in T cells from patients with systemic lupus erythematosus

目的 证实系统性红斑狼疮 (SLE)患者T细胞功能异常是否与其生物化学信号传导异常有关。方法 用CD3单抗与羊抗鼠二抗IgG相交联刺激T细胞并用Thapsigargin和依地酸(EGTA)干预后 ,分别用粘附细胞仪连续观察 10minT细胞 [Ca2 + ]i的变化 ,并评价 [Ca2 + ]i反应与CD3分子和三磷酸肌醇 (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 10 5 ) ;SLE患者高峰值、平台值T细胞的 [Ca2 + ]i反应明显高于正常对照 (P <0 0 0 1,P <0 0 0 1) ;加入Thapsigargin后二者 [Ca2 + ]i反应差异无显著性 ,而加入EGTA后二者[Ca2 + ]i反应差异有显著性 ;二者的T细胞CD3阳性率和InsP3 生成量差异无显著性 (P =0 6 6 5 ,P=0 5 37)。结论 SLE患者T细胞TCR/CD3介导的信号传导途径存在异常 ;

Objective To investigate whether systemic lupus erythematosus (SLE) T cell function disorder is related to abnormal biochemical pathways.Methods After cross linking of anti CD3 mAbs to sheep anti mouse IgG and stimulating T cells,the changes of free calcium ion within T cells and these changes under interference of Thapsigargin and EGTA were observed respectively for 10 minutes with an adhesion cytometry.The relation between [Ca 2+ ]i response in SLE T cells and expression of CD3 molecules,or InsP 3 levels was evaluated.Results The base [Ca 2+ ]i response in T cells of SLE patients was similar to that of 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 groups after addition of Thapsigargin,and [Ca 2+ ]i responses of T cells from SLE patients in the presence of EGTA were higher.Percentages of CD3 + cells and InsP 3 generation were similar in both individuals ( P =0 665, P =0 537).Conclusion TCR/CD3 mediated [Ca 2+ ]i response in T cells from SLE patients is abnormal,and T cell function disorder existing in SLE is the by product of abnormal biochemical pathways.