本文選題：樹突狀細胞 + 轉(zhuǎn)化生長因子-β1�。� 參考：《浙江大學》2005年博士論文

【摘要】：異基因骨髓移植(allo-BMT)是許多惡性、遺傳性血液系統(tǒng)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)仍是異基因骨髓移植中最嚴重的并發(fā)癥,極大地限制了移植的應(yīng)用和療效。雖然人們對急性GVHD的發(fā)病機理有了進一步的認識,然治療仍相當棘手。 目前認為,在急性GVHD發(fā)生過程的第二階段,供者T淋巴細胞與抗原遞呈細胞(APCs)的相互作用后,發(fā)生活化,增殖和分化。受者來源或供者來源的APCs都能將異基因抗原遞呈給供者T淋巴細胞,但受者來源的APCs在急性GVHD的發(fā)生過程中,占主導地位。 樹突狀細胞(dendritic cells,DCs)是功能最強的APCs,不僅能激發(fā)免疫應(yīng)答,同時也參與免疫耐受的誘導,這兩種不同的特性取決于DCs的不同成熟階段。成熟DCs(mDCs)高表達MHC Ⅱ類和共刺激分子,能激發(fā)T淋巴細胞反應(yīng);而未成熟DCs(imDCs)能抑制T淋巴細胞增殖,誘導免疫耐受。ImDCs的這種調(diào)節(jié)功能主要通過直接殺傷T淋巴細胞,誘導T淋巴細胞無能或誘導生成調(diào)節(jié)性T淋巴細胞(Treg)。 轉(zhuǎn)化生長因子β1(TGF-β1)是一種強效的免疫抑制因子,能調(diào)節(jié)多種細胞的增殖和分化。已有研究表明,TGF-β1能抑制DCs成熟,且其處理的DCs(TGFβ-DCs)能顯著延長MHC完全不合小鼠心臟移植的存活時間。 本課題首次提出,在異基因骨髓移植的同時,輸注受者來源的TGFβ-DCs,誘導供者T淋巴細胞產(chǎn)生對受者特異性的免疫耐受,在不用免疫抑制劑的情況下,預(yù)防或減輕急性
[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，

本文編號：1809314