髓样抑制细胞在器官移植中的功能研究

移植耐受维持需多种细胞因子和免疫调节细胞参与，抑制性调节细胞的存在是免疫耐受的主要原因之一。本项目在我们前期工作观察到抗炎性细胞因子和共刺激分子阻断及在（非）致敏移植中作用，髓样抑制细胞（myeloid-derived suppressor cells，MDSCs）与调节T细胞（Tregs）协同参与免疫抑制移植排斥发生的基础上，拟于在体小鼠（非）致敏移植排斥模型上，过继输入MDSCs细胞联合抗炎性细胞因子或共刺激分子阻断剂观察非（致敏）移植物是否能存活延长，离体实验观察MDSCs对效应T细胞增殖抑制的影响，分析早期在体摄入抗IL-4R-alpha中和抗体观察是否能改变Th1/Th2比率，抑制MDSCs形成，从而影响移植物存活，比较（非）致敏移植受体中不同MDSCs细胞亚群基因表达谱的异同，以探讨激活的转录因子和细胞激活相关因子，以期探寻诱导、维持移植免疫耐受的新机制和防治的新策略。

Multiple cytokines and immune regulatory cells are required for the maintenance of transplant tolerance. Regulatory cells with immunosuppressive activity play a critical role in immune tolerance. Our previous observations showed the important role of anti-inflammatory cytokines and costimulatory blockade in the (non-) sensitized transplant models, and that myeloid-derived suppressor cells (MDSCs) and regulatory T cells synergize immunosuppressive function to prevent rejection. Herein, our present study plans to investigate whether adoptive transfer MDSCs in combination with anti-inflammatory or costimulatory blockade treatment could prolong allograft survival in the non-sensitized or sensitized transplant model in mice. The suppressive function of MDSCs on effector T cells proliferation will be analyzed by ex vivo experiments. Furthermore, it will be tested whether early use of anti-IL-4R-alpha neutralizing antibody could alter the ratio of Th1/Th2 and suppress MDSCs production, shortening allograft survival. By comparing gene profiles in different subsets of MDSCs from non-sensitized and sensitized transplant recipients, specific transcript factors and activated cytokines could be characterized. Our present study will provide novel insight into the therapeutic strategies for tolerance induction and maintenance.