TSE1基因在外周T细胞活化、分化及其介导的免疫应答过程中的功能研究

TSE1是本课题组通过EST数据库筛选出的免疫细胞特异性表达的新基因。在之前的青年基金课题中，我们成功制备了TSE1基因敲除小鼠，并证实TSE1在胸腺T细胞的阳性选择过程中发挥重要的作用。本课题将承接以上成果，继续研究TSE1在外周T细胞的活化、分化及其介导不同类型免疫反应过程中的功能。利用初始CD4+ T细胞体外定向分化，探讨TSE1在Th1、Th2、Th17及iTreg等功能亚群分化及其功能发挥中的作用，并结合体内不同类型免疫应答加以验证；通过LCMV病毒感染模型探讨TSE1在CD8+ CTL杀伤过程中的作用，检测相应的CTL杀伤指标；利用小鼠EAE和IBD自身免疫性疾病模型，探讨TSE1在自身免疫性疾病发生过程中的作用，揭示其细胞机制。本课题的完成将在原课题研究的胸腺T细胞发育基础上，进一步阐明TSE1在外周T细胞中的功能，为将TSE1作为临床诊断和治疗T细胞相关疾病的靶点奠定基础。

TSE1 is the T cell specific expressed novel gene found through data mining in ESTs database. We constructed TSE1-/- mice and proved that TSE1 plays an important role during the thymocyte development especially the positive selection. In this study, the function of TSE1 in peripheralna?ve T cells activation and differentiation including Th1, Th2, Th17 and iTreg subsets differentiations will be fully elucidated. We will also introduce different types of immunizations to study the in vivo function of TSE1 during different types of CD4+ T cells-mediated immune responses. Further, we will introduce the Listeria infection model to study the integrated function of TSE1 in different Th cells-mediated responses in vivo. The function of TSE1 in CD8+ CTL cell will be studied using LCMV infection model and the cytotoxic activity will also be detected both in vivo and in vitro. Finally, EAE and IBD disease models will be conducted to elucidate the contributions of TSE1 to the development of autoimmune diseases.