Vav1在吲哚胺2,3双加氧酶抑制T细胞中的作用初探

The role of Vav1 in T cells suppressed by indoleamine 2,3-dioxygenase

目的:探讨吲哚胺2,3双加氧酶(IDO)抑制T细胞中信号传导分子Vav1的分子机制。方法:应用稳定表达IDO的CHO细胞株,与纯化的外周血T细胞共孵育,检测IDO抑制T细胞增殖,诱导凋亡的情况,通过semi-quantitative RT-PCR检测T细胞中Vav1、IL-2 mRNA表达变化;Western blot及免疫沉淀技术检测Vav1蛋白表达及活化情况。结果:IDO可抑制T细胞的增殖。T细胞中Vav1和IL-2 mRNA水平明显下降(P<0.05)。而且,IDO还能使Vav1蛋白的表达和磷酸化水平降低。结论:研究证实在肿瘤局部产生于抗原呈递细胞或肿瘤细胞的IDO,可能通过抑制细胞内重要的信号传导蛋白Vav1的表达和磷酸化过程,使肿瘤浸润淋巴细胞的主动免疫受损,有利于肿瘤发生免疫逃逸。

Objective：To investigate the role of Vavl in T cells suppressed by indoleamine 2,3-dioxygenase. Methods：T-lymphocytes were cocultured with CHO/IDO cells which stably expressed IDO. The proliferation and apoptosis of T cells were detected. The expression levels of Vavl and IL-2 mRNA were determined by semi-quantitative RT-PCR. The expression and activation of Vavl were determined by Western blot and immunoprecipitation. Results： The levels of mRNA and protein of Vavl in T cells both decreased significantly, and the levels of IL-2 mRNA were also reduced after induction with IDO. The tyrosine-phosphorylated Vavl signal sustained for a shorter period in T cells cocultured with CHO/IDO cells than that in peripheral T cells. Conclusion： IDO secreted by the tumor cells or antigen presenting cells could suppress Vavl expression and activation of T cells, which might contribute to tumor immune escape.