CISH基因在人T淋巴细胞分化及抗结核感染中的免疫调节机制研究

明确宿主结核病易感基因与结核病发生发展的关系，是结核病控制领域中研究的重点问题。CISH基因编码的细胞因子诱导的SH2蛋白是细胞因子信号转导负调控蛋白家族的主要成分，因此在调节机体抗结核感染的免疫应答中具有重要的作用。为了进一步明确CISH基因对T淋巴细胞分化以及抗结核感染过程中的免疫调节作用，本项目拟通过构建CISH基因过表达的幼稚T细胞模型，建立CISH基因表达异常的细胞模型，通过对其定向诱导分化，明确CISH基因表达量的改变对T淋巴细胞分化效率的影响；通过对表达异常的幼稚T细胞模型进行结核分枝杆菌攻击实验，明确CISH基因在抗结核感染过程中调节T细胞活化及启动抗炎性免疫应答中的作用机制。该项目将从功能学角度对CISH基因在抗结核感染的过程中的免疫调控作用进行深入全面探究，并可为机体细胞免疫应答研究提供新的数据和理论依据。

Many lines of evidence support an important role of host gene in TB susceptibility and development. CISH (cytokine-inducible SRC homology 2 domain protein) is encoded by the gene called CISH, located at 3p21.3. CISH is a member of the suppressor of cytokine signaling (SOCS) family, which controls the negative feedback of the host immune response. Some researchers have appointed that CISH is critical for T-cell proliferation and survival in response to infection. Therefore, in order to identify the genetic factors of CISH contributing to active TB, the constructed naive CD4+T cell with CISH over-expressing was induced to differentiation, and then the cells was infected with mycobacterium. This study will evaluate the effect of CISH express level on the differentiation and activation of T lymphocyte before and after the infection. Thus, the results of our research will draw a new picture of the host cellular immune response.