受者来源的转化生长因子β1处理的树突状细胞诱导异基因骨髓移植免疫耐受研究

发布时间：2018-04-27 05:10

  本文选题：树突状细胞 + 转化生长因子-β1　； 参考：《浙江大学》2005年博士论文

【摘要】：异基因骨髓移植(allo-BMT)是许多恶性、遗传性血液系统疾病和一些免疫性疾病的可能根治手段。迄今,急性移植物抗宿主病(GVHD)仍是异基因骨髓移植中最严重的并发症,极大地限制了移植的应用和疗效。虽然人们对急性GVHD的发病机理有了进一步的认识,然治疗仍相当棘手。 目前认为,在急性GVHD发生过程的第二阶段,供者T淋巴细胞与抗原递呈细胞(APCs)的相互作用后,发生活化,增殖和分化。受者来源或供者来源的APCs都能将异基因抗原递呈给供者T淋巴细胞,但受者来源的APCs在急性GVHD的发生过程中,占主导地位。 树突状细胞(dendritic cells,DCs)是功能最强的APCs,不仅能激发免疫应答,同时也参与免疫耐受的诱导,这两种不同的特性取决于DCs的不同成熟阶段。成熟DCs(mDCs)高表达MHC Ⅱ类和共刺激分子,能激发T淋巴细胞反应;而未成熟DCs(imDCs)能抑制T淋巴细胞增殖,诱导免疫耐受。ImDCs的这种调节功能主要通过直接杀伤T淋巴细胞,诱导T淋巴细胞无能或诱导生成调节性T淋巴细胞(Treg)。 转化生长因子β1(TGF-β1)是一种强效的免疫抑制因子,能调节多种细胞的增殖和分化。已有研究表明,TGF-β1能抑制DCs成熟,且其处理的DCs(TGFβ-DCs)能显著延长MHC完全不合小鼠心脏移植的存活时间。 本课题首次提出,在异基因骨髓移植的同时,输注受者来源的TGFβ-DCs,诱导供者T淋巴细胞产生对受者特异性的免疫耐受,在不用免疫抑制剂的情况下,预防或减轻急性
[Abstract]:Allogeneic bone marrow transplantation (BMT) is a possible cure for many malignant, hereditary hematological diseases and some immunological diseases. Up to now, acute graft versus host disease (GV HDD) is still the most serious complication in allogeneic bone marrow transplantation, which greatly limits the application and efficacy of allogeneic bone marrow transplantation. Although there has been further understanding of the pathogenesis of acute GVHD, treatment is still tricky. It is suggested that in the second stage of acute GVHD, activation, proliferation and differentiation occur after the interaction between donor T lymphocytes and antigen-presenting cells (APCs). APCs from recipient or donor can present allogeneic antigen to T lymphocytes of donor, but APCs from recipient is dominant in the pathogenesis of acute GVHD. Dendritic cells (DCs) are the most potent APCs, which can not only stimulate immune response but also induce immune tolerance. These two different properties depend on the different maturation stages of DCs. The high expression of MHC class 鈪，

本文编号：1809314