MOLECULAR MECHANISMS OF AUTOIMMUNE DISEASE IN MAN AND ANIMAL MODELS

我们正在研究细胞和分子基础 自身免疫性疾病有两个目的。首先，我们想要确定 致病T细胞的致病作用和抗原特异性 自身免疫性疾病如多发性硬化症、重症肌无力、 胰岛素依赖型糖尿病等。第二，我们希望 为了确定特异性抗原诱导细胞凋亡的可行性， 一种治疗这种自身免疫性疾病的方法。为此，我们 在以下方面取得了进展：1)我们成功地 实验性变态反应猴模型的建立 美国国立卫生研究院的脑脊髓炎；2)我们发现一个重要的 绒猴疾病的组成部分是形成一种 针对绝缘的一种蛋白质成分的致病抗体 中枢神经系统的神经鞘(髓鞘)；3)我们是 为抗原诱导的临床试验迈出第一步 多发性硬化症的细胞凋亡，以及4)我们正在创造一种转基因 建立小鼠重症肌无力模型，以检验其疗效。 抗原诱导的细胞凋亡。作为这些研究的一部分，我们还 试图了解T细胞对抗原诱导死亡的调节 细胞受体刺激。这些研究应该会产生重要的新的 自身免疫性疾病发病机制及治疗的研究进展 疾病在美国是一个普遍的健康问题。 特别是在职业女性中。

We are studying the cellular and molecular basis of autoimmune diseases with two purposes. First, we want to establish the pathogenic role and antigen-specificity of T cells that cause autoimmune diseases such as multiple sclerosis, myasthenia gravis, insulin-dependent diabetes, among others. Second, we would like to determine the feasibility of specific antigen- induced apoptosis as a means of treating such autoimmune diseases. To these ends, we have made progress in the following areas: 1) we have successfully established the marmoset model of experimental allergic encephalomyelitis at the NIH; 2) we found that an important component of the marmoset disease is the formation of a pathogenic antibody against a protein component of the insulating sheath (myelin) of nerves in the central nervous system; 3) we are taking the first steps towards a clinical trial of antigen-induced apoptosis in multiple sclerosis, and 4) we are creating a transgenic mouse model of myasthenia gravis in order to test the efficacy of antigen-induced apoptosis. As part of these studies we are also trying to understand the regulation of antigen-induced death by T cell receptor stimulation. These studies should yield important new insights into the pathogenesis and treatment of autoimmune diseases which is a widespread health problem in the U.S. particularly among working women.