Treg和双基因修饰的imDC诱导肝移植免疫耐受的相互作用机制

项目名称： Treg和双基因修饰的imDC诱导肝移植免疫耐受的相互作用机制

项目编号： No.81202337

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学免疫学、法医学

项目作者： 陈丽红

作者单位： 福建医科大学

项目金额： 23万元

中文摘要： 新型免疫抑制剂使移植器官早期失功的危险性降到较低水平，如何诱导受体抗原特异性免疫低下状态或免疫耐受仍是器官移植追求的理想目标。尽管不成熟树突状细胞（immature dendritic cells, imDC）在诱导免疫耐受中起决定性作用，但调节性T细胞（regulatory T cell, Treg）及相关细胞因子共同参与了移植免疫耐受的过程，它们之间是否存在协同作用及其具体机制有待进一步研究证实。课题组在前期构建IL-10和TGF-β1真核表达载体转染imDC后，显示其在大鼠肝脏的移植模型中具有保护作用。本项目基于前期的研究基础上，深入探讨双基因修饰的imDC是否具有诱导并调节Treg细胞的作用及其可能的作用机制；同时利用已建立的大鼠肝移植模型，将脾脏来源的Treg和双基因共修饰imDC，输入肝移植大鼠体内，探讨二者是否具有协同诱导移植免疫耐受的作用，以期实现寻找持久耐受理想方法。

中文关键词： 树突状细胞；调节性T细胞；IL-10；TGF-β1；肝移植

英文摘要： Immunosuppressive drugs have led to overall improvements in allograft and patient survivals. However,the improved short-term survival rates have come at a cost: these drugs induce many indirect and direct side effects and pose an increased risk of life-threatening complications. These data emphasize the critical role of the recipient's alloimmune response as a major determinant of transplant outcome and highlight the need to develop novel strategies to induce immunologic donor-specific tolerance, defined as a lack of a destructive immune response toward the graft in the presence of generalized immune competence. Regulatory T cells (Treg) and tolerogenic DCs are instrumental in maintaining self-tolerance. In vitro manipulation of these 2 protagonists of the immune response is now emerging as a therapeutic tool to induce tolerance to allotransplantation. Although studies have focused on the development of immature DCs (imDC) as a tool to induce transplant tolerance. Several studies have addressed the significance of Tregs in human transplantation. TGF-β1 and IL-10 signaling seem to be essential for the maintenance of immune homeostasis and suppressing autoimmunity, they are considered to be a key factor in immune tolerance. We do not yet understand when, why and how the human immune system decides to accept the gr

英文关键词： Dendritic cells；Treg；IL–10；TGF-β1；liver transplantation