可诱导共刺激分子通路在同种异体移植免疫中的作用及其机理研究
发布时间：2018-10-14 12:31
【摘要】：本研究共分五个部分:第一部分构建了ICOS-Ig融合蛋白真核表达体系,表达及纯化ICOS-Ig融合蛋白。第二部分对ICOS-Ig融合蛋白的各项理化性质进行了鉴定。第三部分确证ICOS:ICOSL共刺激通路对T细胞免疫功能的正向调节作用,通过体内外实验证实ICOS-Ig竞争性阻断ICOS:ICOSL共刺激通路抑制同种异体T细胞增殖,并可诱导供体特异性T细胞低反应性,即供体特异性免疫耐受。第四部分探讨了ICOSL:ICOS共刺激通路对DC免疫功能可能存在的反向调节作用,ICOS-Ig与DC表达的ICOSL结合,可抑制DC成熟,减弱对同种T细胞的刺激能力,并抑制MAPK信号转导通路的活化。第五部分通过建立小鼠血管化的同种异体心脏移植模型,体内证实ICOS-Ig可明显抑制免疫排斥反应,延长移植物的存活时间,联合CsA可发挥协同作用,进一步实现移植物的长期存活。
[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.
【学位授予单位】：第二军医大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R392
本文编号：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.
【学位授予单位】：第二军医大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R392
【引证文献】
相关博士学位论文 前1条
1 郑晓丽;LIGHT-HVEM共刺激通路在移植物抗宿主病中作用的研究[D];第二军医大学;2008年
，本文编号：2270463
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