整合素相关蛋白（CD47）及其配体对树突状细胞的免疫调控作用及机制研究

发布时间：2018-05-27 21:30

本文选题：树突状细胞 + 免疫耐受　；参考：《浙江大学》2005年博士论文

【摘要】：树突状细胞(DC)是免疫系统强有力的抗原递呈细胞,在免疫应答中起关键的引导和调节作用,其成熟程度、亚群分类决定着免疫激活与免疫耐受之间的平衡,DC的成熟程度为引发T淋巴细胞依赖性免疫应答必需的条件之一。因此,探讨与DC相关的免疫耐受机理已成为移植研究工作者关注的热点之一。抑制性DC是移植免疫学提出的新概念,而未成熟DC则是其中之一。未成熟DC因其低表达协同刺激分子,诱导T淋巴细胞无能及凋亡,在免疫耐受中具有重要的意义。Hirano等报道,在异基因移植动物模型中,输注未成熟DC后不会产生排斥。因此,通过一定的手段诱导产生未成熟DC,使受者建立长期的免疫耐受,可能是一种有前途的治疗手段。 CD47分子是近些年发现的与机体免疫系统、神经系统有密切关系的膜糖蛋白,广泛地表达于所有组织的不同细胞上。已报道,在人DC有CD47抗原表达,本研究结果也显示,人未成熟DC和成熟DC表面均有CD47高表达(94%-98%)。CD47与其配体整合素、信号调节蛋白α(SIRP-α)、凝血酶敏感蛋白(TSP-1)相互作用对机体发挥着多重免疫调控作用,如CD47/SIRP-α可抑制中性粒细胞、单核细胞的迁移及黏附过程:CD47/TSP复合体可诱导T淋巴细胞、DC及单核细胞发生凋亡等,故运用生物手段在体外合成CD47的各种“模拟”配体以干预机体免疫已成为目前许多研究者研究的重点之一。国外有研究报道,采用人工手段合成的各种针对CD47抗原表位的抗体或抗体片段能诱导人T淋巴细胞无能并阻止DC成熟,因此本实验选用B6H12单抗与CD47分子相互作用,以观察是否能干扰DC的分化成
[Abstract]:Dendritic cells (DC) are powerful antigen presenting cells in the immune system, which play a key role in guiding and regulating the immune response. The subgroup classification determines the balance between immune activation and immune tolerance. The maturation of DC is one of the necessary conditions to trigger T lymphocyte dependent immune response. Therefore, the mechanism of immune tolerance related to DC has become one of the hotspots of transplantation researchers. Inhibitory DC is a new concept proposed by transplantation immunology, and immature DC is one of them. Immature DC has important significance in immune tolerance because of its low expression of co-stimulatory molecules, inducing T lymphocyte anergy and apoptosis. In allogeneic transplantation animal model, immature DC does not produce rejection after transfusing immature DC. Therefore, it may be a promising therapeutic method to induce immature DCs and establish long-term immune tolerance. CD47 molecule is a membrane glycoprotein closely related to the immune system and nervous system, which is widely expressed in different cells of all tissues in recent years. It has been reported that CD47 antigen is expressed in human DC. The results of this study also show that both immature and mature DCs have high expression of CD47 and its ligand integrin. The interaction of signal regulated protein 伪 -SIRP- 伪, thrombin sensitive protein (TSP-1) plays a multi-immunoregulatory role in the body, such as CD47% SIRP- 伪 can inhibit neutrophils, The migration and adhesion process of monocytes can induce apoptosis of T lymphocytes, such as DC and monocytes, induced by the 1: CD47 / tsp complex. Therefore, the biosynthesis of various "mimic" ligands of CD47 in vitro to interfere with body immunity has become one of the most important research topics. It has been reported in foreign countries that various antibodies or fragments of antibodies against CD47 epitopes synthesized by artificial means can induce human T lymphocyte incompetence and prevent DC from maturation. Therefore, B6H12 monoclonal antibodies are selected to interact with CD47 molecules. To see if it interferes with DC differentiation.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R392

【共引文献】