临床研究已证实类风湿性关节炎患者在英夫利西单抗治疗后结核发病率显著升高。宿主细胞免疫功能改变是结核病重要发病机制之一。我们的前期研究发现，Vγ2Vδ2+T细胞免疫应答功能在结核免疫发病机制中有重要作用。而新近研究发现英夫利西单抗在体外可抑制γδT细胞免疫反应。因此，我们推测英夫利西单抗参与调控的Vγ2Vδ2+T细胞免疫功能改变在类风关患者结核发病中起关键作用。本课题拟采用病例对照研究比较英夫利西单抗治疗前类风关患者和健康人的γδT细胞免疫功能；然后对使用英夫利西单抗治疗的类风关患者定期随访评估结核发病情况，并以流式细胞检测、磁珠分选、淋巴细胞增殖实验、细胞内细胞因子染色及Real-time PCR等技术对英夫利西单抗如何调控Vγ2Vδ2+T细胞功能进行研究。本课题研究结果将初步阐明Vγ2Vδ2+T细胞功能改变在类风关患者结核发病中的免疫作用机制，有望开发以该细胞为靶位的新型抗结核免疫策略。

The reported frequency of tuberculosis among rheumatoid arthritis (RA) patients treated with infliximab was significantly higher than the available background rates.As we know, the change of host cellullar immune function is one of the major pathogenesis of tuberculosis. Our previous study in patients with latent and active tuberculosis has found that Vγ2Vδ2+T cells contribute to protective immune response against Mycobacterium tuberculosis. Recently, it has been reported that the immune response of Vγ2Vδ2+T cells from RA patients was inhibited by the exposure to infliximab in vitro. Therefore, we hypothesize that increasing frequency of tuberculosis among RA patients might be of great relevance with the immune functional changes of Vγ2Vδ2+T cells regulated by TNF-alpha blocker infliximab. To prove this hypothesis, a case control study will be designed to evaluate the immune response of Vγ2Vδ2+T cells from healthy controls and from RA patients prior to initiation of infliximab therapy. Then the RA patients receiving infliximab therapy will be regular followed to assess TB incidence and the immune functional changes of Vγ2Vδ2+T cells in vivo. Flow cytometry, MACS cell separation, lymphocyte proliferation, intracellular cytokine staining (ICS) and real-time PCR will be employed to investigate the effect of TNF-alpha blocker infliximab on the immune function of Vγ2Vδ2+T cells and to interpret the immunopathogenesis of tuberculosis among RA patients receiving treatment with infliximab. These results will help to develope a new immunotherapeutic strategy for tuberculosis among RA patients.