TIM-1-Fc介导辅助T淋巴细胞反应调控异位小肠移植免疫应答机制的研究

项目名称： TIM-1-Fc介导辅助T淋巴细胞反应调控异位小肠移植免疫应答机制的研究

项目编号： No.81671581

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 医药、卫生

项目作者： 宋京海

作者单位： 北京医院

项目金额： 25万元

中文摘要： 小肠移植物富含大量的活性淋巴细胞并分泌高水平的促炎症因子是导致排斥（rejection）和移植物抗宿主（GVHD）免疫反应的重要原因，阻断T细胞共刺激信号通路可能对控制免疫反应的发生发展发挥重要作用。新近发现T细胞免疫球蛋白及粘蛋白结构域分子蛋白1(TIM-1)是一种最初发现于活化的Th2细胞表面的共刺激分子，TIM-1分子在维护体内Th免疫平衡稳定中起重要作用。阻断TIM-1的生物效应能否参与小肠移植免疫应答的发生尚不清楚。我们检测合成的人源化TIM-1-Fc融合蛋白在体外供体来源的T淋巴细胞免疫反应的影响，利用大鼠小肠移植模型进一步认识TIM-1-Fc分子在T细胞介导的免疫反应和抑制同种移植物rejection 和GVHD反应中调节T淋巴细胞的作用机制，为寻找临床器官移植，特别是小肠移植免疫抑制治疗的新靶点提供实验依据。

中文关键词： T；细胞免疫球蛋白及粘蛋白结构域相关分子蛋白-1；小肠移植；免疫反应；辅助T细胞；大鼠

英文摘要： Small intestinal grafts are rich in a large number of active lymphocytes, which secrete high levels of pro-inflammatory cytokines, which are important factors leading to rejection and graft versus host disease immune responses. Blocking T cell costimulatory signal pathway on immune responses to control the occurrence and development play an important role. The newly discovered T cell immunoglobulin and mucin domain protein 1 (TIM-1) is a costimulatory molecule originally found on the surface of activated Th2 cells, the TIM-1 molecules play an important role in the maintenance of Th in the immune balance and stability. Blocking the biological effects of TIM-1 can participate in small bowel transplantation immune response occurs is unclear. We detected T lymphocyte immune response humanized synthesis of TIM-1-Fc fusion protein in vitro donor, the rat model of intestinal transplantation to further understanding of the TIM-1-Fc molecules in T cell mediated immunity against The role of T and GVHD in the regulation of rejection lymphocytes in the response of the same graft should be suppressed to provide experimental evidence for finding new targets for clinical organ transplantation, especially for the immunosuppressive therapy of small intestinal transplantation.

英文关键词： T cell immungolbulin and mucin domain protein 1 ;small bowel transplantation;immuno reaction;T helper cell;rat