【摘要】：本研究共分五個部分:第一部分構(gòu)建了ICOS-Ig融合蛋白真核表達體系,表達及純化ICOS-Ig融合蛋白。第二部分對ICOS-Ig融合蛋白的各項理化性質(zhì)進行了鑒定。第三部分確證ICOS:ICOSL共刺激通路對T細胞免疫功能的正向調(diào)節(jié)作用,通過體內(nèi)外實驗證實ICOS-Ig競爭性阻斷ICOS:ICOSL共刺激通路抑制同種異體T細胞增殖,并可誘導(dǎo)供體特異性T細胞低反應(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DC免疫功能可能存在的反向調(diào)節(jié)作用,ICOS-Ig與DC表達的ICOSL結(jié)合,可抑制DC成熟,減弱對同種T細胞的刺激能力,并抑制MAPK信號轉(zhuǎn)導(dǎo)通路的活化。第五部分通過建立小鼠血管化的同種異體心臟移植模型,體內(nèi)證實ICOS-Ig可明顯抑制免疫排斥反應(yīng),延長移植物的存活時間,聯(lián)合CsA可發(fā)揮協(xié)同作用,進一步實現(xiàn)移植物的長期存活。
[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)位級別】：博士
【學(xué)位授予年份】：2006
【分類號】：R392

【引證文獻】

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

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本文編號：2270463