SUPPRESSOR MECHANISMS REGULATING AUTOIMMUNE THYROIDITIS

小鼠实验性自身免疫性甲状腺炎（EAT）是一种 桥本甲状腺炎研究的原型，以及 其他器官特异性自身免疫性疾病。 的总目标 本项目是利用小鼠EAT来探测抑制基因， 导致甲状腺功能障碍的机制。 就像人类一样， 自身免疫反应受遗传控制 甲状腺肿大 抗原是甲状腺球蛋白（Tg），它可以用来诱导EAT， 遗传易感菌株，与主要的 组织相容性复合体（MHC）。 最近的三个观察 来自我们实验室的科学家们为这一提议提供了动力：1） 自身耐受性通过预先给予 外源性MTg耐受免疫原性攻击是介导的 2）增强对EAT诱导的抗性， 也可以通过生理操纵循环MTg来实现 与甲状腺调节激素水平;和3）体内选择性 高效大鼠单克隆抗体消除T细胞亚群 抗L3 T4和Lyt-2抗体（mAb）可预防或改变EAT 归纳和发展。 我们建议：1. 刻画， 在体外和体内，抑制性T细胞被激活， 给予外源性MTg。 2. 确定函数 抗L3 T4 mAb增强EAT抗性的能力， 重建自我宽容。 3. 检查抑制器 促甲状腺激素（TSH）激活的机制。

Experimental autoimmune thyroiditis (EAT) in mice serves as a prototype for the study of Hashimoto's thyroiditis, as well as other organ-specific autoimmune disorders. The overall goal of this project is to use murine EAT to probe the suppressor mechanisms leading to thyroid dysfunction. As in the human, the autoimmune response is under genetic control. A major thyroid antigen is thyroglobulin (Tg) which can be used to induce EAT in genetically susceptible strains, linked to the major histocompatibility complex (MHC). Three recent observations from our laboratory have provided impetus to this proposal: 1) Self tolerance strengthened by the prior administration of exogenous MTg to withstand immunogenic challenge is mediated by suppressor T cells; 2) enhanced resistance to EAT induction can also be achieved by physiologic manipulation of circulatory MTg level with thyroid-regulating hormones; and 3) selective in vivo elimination of T cell subsets with highly efficient rat monoclonal antibodies (mAb) to L3T4 and Lyt-2 prevents or modifies EAT induction and development. We propose to: 1. Characterize, both in vitro and in vivo, suppressor T cells activated by the administration of exogenous MTg. 2. Determine the functional capabilities of mAb to L3T4 in enhancing resistance to EAT and re-establishing self tolerance. 3. Examine suppressor mechanisms activated by thyroid-stimulating hormone (TSH).