Molecular Mechanisms Of Autoimmune Disease In Man And An

我们研究自身免疫性疾病的细胞和分子基础有两个目的。首先，我们希望确定引起自身免疫性疾病（如多发性硬化症、重症肌无力、胰岛素依赖型糖尿病等）的T细胞的致病作用和抗原特异性。其次，我们想确定特异性抗原诱导细胞凋亡作为治疗这类自身免疫性疾病的一种手段的可行性。为此，我们在以下方面取得了进展：1)我们建立了一种转基因T细胞受体小鼠模型，该模型对乙酰胆碱受体的肽有强烈的反应；2)我们正在研究与自身免疫相关的凋亡相关基因，以确定自身免疫的遗传决定因素；3)我们正在启动抗原特异性治疗的研究，以防止血友病患者在给予因子VIII后形成阻断抗体。作为这些研究的一部分，我们还试图了解T细胞受体刺激对抗原诱导死亡的调节。这些研究应该为自身免疫性疾病的发病机制和治疗提供重要的新见解，这是一个普遍存在的健康问题，尤其是在美国的职业女性中。

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-of ainduced apoptosis as a means of treating such autoimmune diseases. To these ends, we have made progress in the following areas: 1) we have characterized a transgenic T cell receptor mouse model of myasthenia gravis which has a powerful response to a peptide from the acetylcholine receptor; 2) we are studying sets of apoptosis-related genes for association with autoimmunity to establish genetic determinants of autoimmunity; and 3) we are initiating studies of antigen-specific therapy to prevent the formation of blocking antibodies following factor VIII administration to hemophiliacs. 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.