胸腺移植诱导小鼠半相合骨髓移植后免疫耐受及促进免疫重建的研究
发布时间：2018-10-05 14:30
【摘要】：研究背景和目的 造血干细胞移植(HSCT)尤其是异基因HSCT(allo-HSCT)现广泛应用于血液肿瘤或非血液恶性肿瘤、再生障碍性贫血、某些遗传性疾病等的治疗。由于目前尚未解决的高移植物抗宿主病(GVHD)和高机会性感染率与致死率，致使allo-HSCT后患者的长期生存率仅在50％左右，同时因移植后GVHD和机会性感染而影响患者的生存质量。解决allo-HSCT后GVHD和降低机会性感染的发生率与致死率是提高allo-HSCT后长期无病生存和生活质量的关键。在allo-HSCT中，诱导供者T细胞对受者抗原产生免疫耐受及促进移植后T细胞的重建，，是目前提高allo-HSCT后长期无病生存和生活质量的关键。 在个体发育过程中，T细胞获得对自身抗原的免疫耐受和T细胞受体(TCR)库的形成主要在胸腺完成，它依赖于胸腺上皮细胞及微环境。在不同年龄的allo-HSCT患者中观察到，随着受者年龄增长，GVHD的发生率和机会性感染率均增高，免疫重建延迟越明显。allo-HSCT后儿童患者可在移植后大约一年内完成以T细胞为基础的免疫重建，成人则需要数年甚至终生不能重建完整的T细胞库，这些都与随着年龄的增长，胸腺逐渐萎缩，对供者T细胞的修饰作用(胸腺选择)降低有关。allo-HSCT后供者T细胞的重建主要通过胸腺依赖途径和胸腺非依赖途径完成。allo-HSCT后受者体内存在5类不同类型的T细胞群落，其
[Abstract]:Background and objective Hematopoietic stem cell transplantation (HSCT), especially allogeneic HSCT (allo-HSCT), has been widely used in hematopoietic neoplasms, non-hematological malignancies and aplastic anemia. The treatment of certain hereditary diseases, etc. Because of the unsolved high graft-versus-host disease (GVHD), high opportunistic infection rate and fatality rate, the long-term survival rate of patients with allo-HSCT was only about 50%, and the quality of life was affected by GVHD and opportunistic infection after transplantation. To solve the problem of GVHD after allo-HSCT and to reduce the incidence and mortality of opportunistic infection is the key to improve the long-term disease-free survival and quality of life after allo-HSCT. In allo-HSCT, the key to improve the long-term disease-free survival and quality of life after allo-HSCT is to induce donor T cells to develop immune tolerance to the recipient antigen and to promote the reconstruction of T cells after transplantation. The immune tolerance of T cells to autoantigen and the formation of T cell receptor (TCR) library are mainly completed in the thymus, which is dependent on thymoepithelial cells and microenvironment. It was observed that the incidence and opportunistic infection rate of allo-HSCT increased with the age of the recipient. The more significant the delay in immune reconstruction. Allo-HSCT in children can complete T cell-based immune reconstruction within about one year after transplantation, and in adults it takes years or even lifetime to reconstruct a complete T cell bank, which is associated with age. The thymus shrinks gradually, The modification of donor T cells (thymus selection) is related to the reduction of donor T cell remodeling after. Allo-HSCT. There are five different types of T cell communities in the recipient by thymus dependent pathway and thymus independent pathway.
【学位授予单位】：第一军医大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R392.4
本文编号：2253758
[Abstract]:Background and objective Hematopoietic stem cell transplantation (HSCT), especially allogeneic HSCT (allo-HSCT), has been widely used in hematopoietic neoplasms, non-hematological malignancies and aplastic anemia. The treatment of certain hereditary diseases, etc. Because of the unsolved high graft-versus-host disease (GVHD), high opportunistic infection rate and fatality rate, the long-term survival rate of patients with allo-HSCT was only about 50%, and the quality of life was affected by GVHD and opportunistic infection after transplantation. To solve the problem of GVHD after allo-HSCT and to reduce the incidence and mortality of opportunistic infection is the key to improve the long-term disease-free survival and quality of life after allo-HSCT. In allo-HSCT, the key to improve the long-term disease-free survival and quality of life after allo-HSCT is to induce donor T cells to develop immune tolerance to the recipient antigen and to promote the reconstruction of T cells after transplantation. The immune tolerance of T cells to autoantigen and the formation of T cell receptor (TCR) library are mainly completed in the thymus, which is dependent on thymoepithelial cells and microenvironment. It was observed that the incidence and opportunistic infection rate of allo-HSCT increased with the age of the recipient. The more significant the delay in immune reconstruction. Allo-HSCT in children can complete T cell-based immune reconstruction within about one year after transplantation, and in adults it takes years or even lifetime to reconstruct a complete T cell bank, which is associated with age. The thymus shrinks gradually, The modification of donor T cells (thymus selection) is related to the reduction of donor T cell remodeling after. Allo-HSCT. There are five different types of T cell communities in the recipient by thymus dependent pathway and thymus independent pathway.
【学位授予单位】：第一军医大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R392.4
【参考文献】
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1 邵传森,朱康儿,郭汉身;同种异基因小鼠外周血干细胞移植的初步研究[J];中华血液学杂志;1997年05期
本文编号：2253758
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