INDUCTION OF TRANSPLANTATION TOLERANCE BY ORAL ROUTE

成功的移植取决于国家的发展 对移植物的不相容同种抗原的耐受性， 尤其是MHC系统的那些。 目前诊所的状况 是一个短期的tcrm成功，但国家的宽容不需要 使用强效和毒性免疫抑制剂 容易实现。 肠道有一个复杂的免疫系统 这是不完全理解的。 虽然口服途径可以 用于免疫接种，有许多实验性的例子， 耐受诱导，包括预防或治疗自身免疫性 动物模型中的疾病。 据报道， 关于移植。 分子生物学和 MHC分子的结构，以及改进的 效应子和调节子的功能多样性的定义 T细胞，现在可以进行实验， 了解如何利用肠道免疫 系统的能力，以影响免疫反应，在一个消极的 方向 代表多态性区域的合成肽 大鼠II类MHC已被证明口服后，部分 以抗原特异性方式在体外和体内耐受T细胞。 这项研究的目的是要解决的关系问题， 在MHC肽的免疫原性和耐受原性之间， 关于T细胞无反应性与抑制的作用， 肠上皮细胞增殖反应的独特性 上皮T细胞与上皮T细胞的肽提呈能力 细胞，并优化口服喂养延长 同种异体移植 将使用大鼠和小鼠鼠模型，包括 Mls免疫耐受和T细胞受体转基因小鼠 小鼠 涉及细胞因子的机制， 下调功能（例如，TGF β、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.