可誘導(dǎo)共刺激分子通路在同種異體移植免疫中的作用及其機(jī)理研究
發(fā)布時(shí)間：2018-10-14 12:31
【摘要】：本研究共分五個(gè)部分:第一部分構(gòu)建了ICOS-Ig融合蛋白真核表達(dá)體系,表達(dá)及純化ICOS-Ig融合蛋白。第二部分對(duì)ICOS-Ig融合蛋白的各項(xiàng)理化性質(zhì)進(jìn)行了鑒定。第三部分確證ICOS:ICOSL共刺激通路對(duì)T細(xì)胞免疫功能的正向調(diào)節(jié)作用,通過(guò)體內(nèi)外實(shí)驗(yàn)證實(shí)ICOS-Ig競(jìng)爭(zhēng)性阻斷ICOS:ICOSL共刺激通路抑制同種異體T細(xì)胞增殖,并可誘導(dǎo)供體特異性T細(xì)胞低反應(yīng)性,即供體特異性免疫耐受。第四部分探討了ICOSL:ICOS共刺激通路對(duì)DC免疫功能可能存在的反向調(diào)節(jié)作用,ICOS-Ig與DC表達(dá)的ICOSL結(jié)合,可抑制DC成熟,減弱對(duì)同種T細(xì)胞的刺激能力,并抑制MAPK信號(hào)轉(zhuǎn)導(dǎo)通路的活化。第五部分通過(guò)建立小鼠血管化的同種異體心臟移植模型,體內(nèi)證實(shí)ICOS-Ig可明顯抑制免疫排斥反應(yīng),延長(zhǎng)移植物的存活時(shí)間,聯(lián)合CsA可發(fā)揮協(xié)同作用,進(jìn)一步實(shí)現(xiàn)移植物的長(zhǎng)期存活。
[Abstract]:This study was divided into five parts: in the first part, the eukaryotic expression system of ICOS-Ig fusion protein was constructed, and the ICOS-Ig fusion protein was expressed and purified. In the second part, the physicochemical properties of ICOS-Ig fusion protein were identified. In the third part, the positive regulation of ICOS:ICOSL costimulatory pathway on T cell immune function was confirmed. In vivo and in vitro, it was proved that ICOS-Ig could block the ICOS:ICOSL co-stimulation pathway to inhibit the proliferation of allogeneic T cells. And can induce donor-specific T-cell hyporesponsiveness, that is, donor-specific immune tolerance. In the fourth part, we discuss the reverse regulation of ICOSL:ICOS costimulatory pathway on the immune function of DC. The combination of ICOS-Ig and DC can inhibit the maturation of DC, weaken the stimulation ability of T cells and inhibit the activation of MAPK signal transduction pathway. In the fifth part, by establishing a vascularized allograft heart transplantation model in mice, it was proved in vivo that ICOS-Ig could significantly inhibit immune rejection, prolong the survival time of grafts, and combine with CsA to play a synergistic effect. Further realize the long-term survival of the graft.
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2006
【分類號(hào)】：R392
本文編號(hào)：2270463
[Abstract]:This study was divided into five parts: in the first part, the eukaryotic expression system of ICOS-Ig fusion protein was constructed, and the ICOS-Ig fusion protein was expressed and purified. In the second part, the physicochemical properties of ICOS-Ig fusion protein were identified. In the third part, the positive regulation of ICOS:ICOSL costimulatory pathway on T cell immune function was confirmed. In vivo and in vitro, it was proved that ICOS-Ig could block the ICOS:ICOSL co-stimulation pathway to inhibit the proliferation of allogeneic T cells. And can induce donor-specific T-cell hyporesponsiveness, that is, donor-specific immune tolerance. In the fourth part, we discuss the reverse regulation of ICOSL:ICOS costimulatory pathway on the immune function of DC. The combination of ICOS-Ig and DC can inhibit the maturation of DC, weaken the stimulation ability of T cells and inhibit the activation of MAPK signal transduction pathway. In the fifth part, by establishing a vascularized allograft heart transplantation model in mice, it was proved in vivo that ICOS-Ig could significantly inhibit immune rejection, prolong the survival time of grafts, and combine with CsA to play a synergistic effect. Further realize the long-term survival of the graft.
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2006
【分類號(hào)】：R392
【引證文獻(xiàn)】
相關(guān)博士學(xué)位論文 前1條
1 鄭曉麗;LIGHT-HVEM共刺激通路在移植物抗宿主病中作用的研究[D];第二軍醫(yī)大學(xué);2008年
，本文編號(hào)：2270463
本文鏈接：http://sikaile.net/yixuelunwen/binglixuelunwen/2270463.html
最近更新
教材專著
