Wang Guanming, Yan Yuhui, Chen Xiaohua, Lin Chen, Li Yangqiu
Department of Microbiology and Immunology, Medical College, Jinan University, Guangzhou 510632, China ; Quanzhou Medical college, Quanzhou 362000, China.
Department of Microbiology and Immunology, Medical College, Jinan University, Guangzhou 510632, China.
Biomed Res Int. 2014;2014:682010. doi: 10.1155/2014/682010. Epub 2014 Jan 2.
The BCR-ABL kinase inhibitor imatinib is highly effective in the treatment of chronic myeloid leukemia (CML). However, long-term imatinib treatment induces immunosuppression, which is mainly due to T cell dysfunction. Imatinib can reduce TCR-triggered T cell activation by inhibiting the phosphorylation of tyrosine kinases such as Lck, ZAP70, LAT, and PLC γ 1 early in the TCR signaling pathway. The purpose of this study was to investigate whether the superantigen SEA, a potent T cell stimulator, can block the immunosuppressive effects of imatinib on T cells. Our data show that the exposure of primary human T cells and Jurkat cells to SEA for 24 h leads to the upregulation of the Lck and ZAP70 proteins in a dose-dependent manner. T cells treated with SEA prior to TCR binding had increased the tyrosine phosphorylation of Lck, ZAP70, and PLC γ 1. Pretreatment with SEA prevents the inhibitory effects of imatinib on TCR signaling, which leads to T cell proliferation and IL-2 production. It is conceivable that SEA antagonizes the imatinib-mediated inhibition of T cell activation and proliferation through the TCR signaling pathway.
BCR-ABL激酶抑制剂伊马替尼在慢性粒细胞白血病（CML）治疗中疗效显著。然而，长期使用伊马替尼治疗会引发免疫抑制，这主要是由于T细胞功能障碍所致。伊马替尼可通过抑制TCR信号通路早期的酪氨酸激酶（如Lck、ZAP70、LAT和PLCγ1）磷酸化，来降低TCR触发的T细胞活化。本研究旨在探究超抗原SEA（一种强效T细胞刺激剂）是否能够阻断伊马替尼对T细胞的免疫抑制作用。我们的数据表明，原代人T细胞和Jurkat细胞暴露于SEA 24小时会导致Lck和ZAP70蛋白呈剂量依赖性上调。在TCR结合之前用SEA处理的T细胞，其Lck、ZAP70和PLCγ1的酪氨酸磷酸化增加。SEA预处理可防止伊马替尼对TCR信号传导的抑制作用，进而导致T细胞增殖和IL-2产生。可以想象，SEA通过TCR信号通路拮抗伊马替尼介导的T细胞活化和增殖抑制。
