CD137在内皮细胞的表达及功能研究

发布时间：2018-01-02 09:22

本文关键词：CD137在内皮细胞的表达及功能研究　出处：《第三军医大学》2005年博士论文　论文类型：学位论文

【摘要】： 血管内皮细胞(Endothelial cell , EC)的免疫功能日益受到重视,内皮细胞除了保证血管壁结构与功能完整,激活后还可表达或上调表达多种免疫功能相关分子,既可作为细胞因子、炎性因子作用的靶细胞,又能分泌细胞因子等活性介质,在机体的炎症反应和免疫应答过程中有重要作用。它具有多种免疫功能,与许多疾病的发生、发展有密切的关系。 EC以MHC-Ⅱ类分子限制性方式将抗原肽呈递给淋巴细胞,并可通过B7/ CD28、CD40/ CD40L、CD58(LFA-3)/ CD2(LFA-2)等途径向淋巴细胞提供共刺激信号,促进免疫应答的进程。EC上表达的共刺激分子(LFA-3、CD40L、PDL-1、PDL-2、ICOSL、OX40L)和T细胞上表达的相应的受体结合后,一方面可以作用于EC而促使其活化和分泌细胞因子,另一方面又可以影响CD4+T淋巴细胞和CD8+T淋巴细胞活化和功能,从而参与特异性免疫应答的调控以及增强细胞因子的分泌。所以,共刺激分子在EC与T细胞的相互作用中发挥着重要的作用。研究发现,共刺激分子在免疫应答的不同阶段介导免疫应答的启动、激发、扩大和增强作用以及效应介导,而且通过负性共刺激分子可精确地调节应答的程度和持续的时间。效应性CD8+和CD4+T细胞的维持和功能,以及记忆性T细胞发生再次应答不依赖B7-1/B7-2-CD28/CTLA-4和CD40-CD40L共刺激信号通路,针对调节记忆和效应性T细胞的功能达到维持外周耐受应选择ICOS-B7RP-1和PD-1-PD-L1/PD-L2信号通路,但是,有时ICOS-B7RP-1或PD-1-PD-L1/PD-L2信号通路不能完全抑制CD8+T细胞的功能,而CD137在调节CD8+T细胞的功能方面有着重要的作用。我们初步研究证实,内皮细胞在未活化时有较低的CD137蛋白表达,内皮细胞活化后CD137的表达上调。CD137是肿瘤坏死因子受体(TNFR)家族的成员之一,它表达于活化的T细胞表面,介导的协同刺激信号能促进T细胞活化、增殖、分化,也能诱导T细胞凋亡。CD137既能协同CD28对T细胞的共刺激作用,也能不依赖于CD28而发挥共刺激效应。另外,CD137也表达于DC和单核细胞,并促进DC和单核细胞
[Abstract]:The immune function of vascular endothelial cells ( EC ) has been paid more and more attention . In addition to ensuring that the structure and function of the vessel wall are intact , the endothelial cells can express or up - regulate the expression of various immune function - related molecules after activation , which can be used as a target cell for the action of cytokines and inflammatory factors , and can secrete cytokines and other active media . It has various immune functions , and has a close relationship with the occurrence and development of many diseases . On the other hand , the co - stimulatory molecules play an important role in the interaction of EC and T cells . It was found that co - stimulatory molecules mediate the initiation , excitation , amplification and enhancement of immune responses at different stages of immune response , as well as the effect - mediated , and the extent and duration of the response can be precisely adjusted by negative costimulatory molecules . The effects of effector CD8 + and CD4 + T cells and the re - response of memory T cells do not depend on B7 - 1 / B7 - 2 - CD28 / T - 4 and CD40 - CD40L co - stimulatory signal pathways , but sometimes the function of CD8 + T cells can not be completely inhibited by ICOS - BRP - 1 or PD - 1 - PD - L1 / PD - L2 signaling pathways , while CD137 plays an important role in regulating the function of CD8 + T cells . CD137 is a member of the tumor necrosis factor receptor ( TNFR ) family . CD137 is a member of the tumor necrosis factor receptor ( TNFR ) family .

【学位授予单位】：第三军医大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R392

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