INDUCTION OF TRANSPLANTATION TOLERANCE BY ORAL ROUTE

成功的移植取决于一个国家的发展 对移植物不相容的同种异体抗原的耐受性， 尤其是MHC系统的那些。临床上的现状 是一种短暂的tcrm成功，但宽容的状态不需要 使用强效和有毒的免疫抑制剂并不是 很容易就能实现。肠道有一个复杂的免疫系统。 这一点还不能完全理解。尽管口服途径可以是 用于免疫的，有许多实验例子 诱导耐受，包括预防或治疗自身免疫 动物模型中的疾病。几乎没有关于这方面的报道 关于移植。分子生物学和分子生物学的研究进展 MHC的分子结构以及改进 效应器和调节剂功能种类的界定 T细胞，现在使进行实验成为可能 介绍如何利用肠道免疫的知识 系统对免疫反应产生负面影响的能力 方向。代表多态区域的合成肽 大鼠第二类MHC在部分口服后表现出 在体外和体内以抗原特异性的方式耐受T细胞。 这项研究的目的是解决两国关系的问题 在MHC多肽的免疫原性和耐受性之间，模式 关于T细胞无能与抑制的作用， 肠道增殖性反应的唯一性 上皮性T细胞与上皮性T细胞的肽递呈能力 细胞，并优化口服喂养，以延长 异体移植。将使用大鼠和小鼠模型，包括 小鼠对MLS免疫耐受及T细胞受体转基因 老鼠。涉及潜在细胞因子的机制 将追求下调功能(例如，TGFbeta、IL-4、IL-10)。

Successful transplantation depends upon the development of a state of tolerance to the incompatible alloantigens of the graft, especially those of the MHC system. The current state in the clinic is one of short tcrm success, but states of tolerance not requiring the use of powerful and toxic immunosuppressive agents are not easily achievable. The intestine has an elaborate immune system which is incompletely understood. Although the oral route can be used for immunization, there are many experimental examples of tolerance induction, including prevention or treatment of autoimmune disease in animal models . There has been little reported with regard to transplantation. Advances in the molecular biology and structure of the molecules of the MHC, as well as improved definition of the functional varieties of effector and regulatory T cells, now make it possible to perform experiments which should lead to knowledge on how to take advantage of the intestinal immune system's abilities to influence immune responses in a negative direction. Synthetic peptides representing the polymorphic regions of rat class II MHC have been shown after oral feeding to partially tolerize T cells in vitro and in vivo in an antigen specific manner. The study will aim to address the questions of the relationship between immunogenicity and tolerogenicity of MHC peptides, the mode of action with regard to T cell anergy versus suppression, the uniqueness of the proliferative responses of the intestinal epithelial T cells and the peptide presenting capacity of epithelial cells, and optimization of oral feeding to the prolongation of allografts. Rat and mouse murine models will be used, including mice tolerized to Mls immunization and T cell receptor transgenic mice. Mechanisms which involve cytokines with potential downregulatory function (e.g., TGFbeta, IL-4,IL-10) will be pursued.