CD137在內(nèi)皮細(xì)胞的表達(dá)及功能研究
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本文關(guān)鍵詞:CD137在內(nèi)皮細(xì)胞的表達(dá)及功能研究 出處:《第三軍醫(yī)大學(xué)》2005年博士論文 論文類型:學(xué)位論文
更多相關(guān)文章: CD137 CD137L TNFR 內(nèi)皮細(xì)胞 共刺激分子 細(xì)胞因子 免疫功能 白介素 黏附分子 RT-PCR APC
【摘要】: 血管內(nèi)皮細(xì)胞(Endothelial cell , EC)的免疫功能日益受到重視,內(nèi)皮細(xì)胞除了保證血管壁結(jié)構(gòu)與功能完整,激活后還可表達(dá)或上調(diào)表達(dá)多種免疫功能相關(guān)分子,既可作為細(xì)胞因子、炎性因子作用的靶細(xì)胞,又能分泌細(xì)胞因子等活性介質(zhì),在機(jī)體的炎癥反應(yīng)和免疫應(yīng)答過程中有重要作用。它具有多種免疫功能,與許多疾病的發(fā)生、發(fā)展有密切的關(guān)系。 EC以MHC-Ⅱ類分子限制性方式將抗原肽呈遞給淋巴細(xì)胞,并可通過B7/ CD28、CD40/ CD40L、CD58(LFA-3)/ CD2(LFA-2)等途徑向淋巴細(xì)胞提供共刺激信號(hào),促進(jìn)免疫應(yīng)答的進(jìn)程。EC上表達(dá)的共刺激分子(LFA-3、CD40L、PDL-1、PDL-2、ICOSL、OX40L)和T細(xì)胞上表達(dá)的相應(yīng)的受體結(jié)合后,一方面可以作用于EC而促使其活化和分泌細(xì)胞因子,另一方面又可以影響CD4+T淋巴細(xì)胞和CD8+T淋巴細(xì)胞活化和功能,從而參與特異性免疫應(yīng)答的調(diào)控以及增強(qiáng)細(xì)胞因子的分泌。所以,共刺激分子在EC與T細(xì)胞的相互作用中發(fā)揮著重要的作用。 研究發(fā)現(xiàn),共刺激分子在免疫應(yīng)答的不同階段介導(dǎo)免疫應(yīng)答的啟動(dòng)、激發(fā)、擴(kuò)大和增強(qiáng)作用以及效應(yīng)介導(dǎo),而且通過負(fù)性共刺激分子可精確地調(diào)節(jié)應(yīng)答的程度和持續(xù)的時(shí)間。效應(yīng)性CD8+和CD4+T細(xì)胞的維持和功能,以及記憶性T細(xì)胞發(fā)生再次應(yīng)答不依賴B7-1/B7-2-CD28/CTLA-4和CD40-CD40L共刺激信號(hào)通路,針對(duì)調(diào)節(jié)記憶和效應(yīng)性T細(xì)胞的功能達(dá)到維持外周耐受應(yīng)選擇ICOS-B7RP-1和PD-1-PD-L1/PD-L2信號(hào)通路,但是,有時(shí)ICOS-B7RP-1或PD-1-PD-L1/PD-L2信號(hào)通路不能完全抑制CD8+T細(xì)胞的功能,而CD137在調(diào)節(jié)CD8+T細(xì)胞的功能方面有著重要的作用。 我們初步研究證實(shí),內(nèi)皮細(xì)胞在未活化時(shí)有較低的CD137蛋白表達(dá),內(nèi)皮細(xì)胞活化后CD137的表達(dá)上調(diào)。CD137是腫瘤壞死因子受體(TNFR)家族的成員之一,它表達(dá)于活化的T細(xì)胞表面,介導(dǎo)的協(xié)同刺激信號(hào)能促進(jìn)T細(xì)胞活化、增殖、分化,也能誘導(dǎo)T細(xì)胞凋亡。CD137既能協(xié)同CD28對(duì)T細(xì)胞的共刺激作用,也能不依賴于CD28而發(fā)揮共刺激效應(yīng)。另外,CD137也表達(dá)于DC和單核細(xì)胞,并促進(jìn)DC和單核細(xì)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 .
【學(xué)位授予單位】:第三軍醫(yī)大學(xué)
【學(xué)位級(jí)別】:博士
【學(xué)位授予年份】:2005
【分類號(hào)】:R392
【參考文獻(xiàn)】
相關(guān)期刊論文 前1條
1 陳純,黃紹良,段連寧,李浩威,溫冠媚,魏菁;阻斷CD40-CD40L共刺激途徑對(duì)T細(xì)胞表型及細(xì)胞因子分泌的作用研究[J];中國(guó)免疫學(xué)雜志;2003年08期
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