Molecular Mechanisms Of Autoimmune Disease In Man/Animal

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，我们想确定T细胞的致病作用和抗原特异性，这些T细胞会导致自身免疫性疾病，如多发性硬化症、重症肌无力、胰岛素依赖型糖尿病等。其次，我们想确定特异性抗原诱导的细胞凋亡作为治疗这种自身免疫性疾病的手段的可行性。为此，我们在以下领域取得了进展：1）我们已经表征了对乙酰胆碱受体肽具有强烈反应的转基因重症肌无力T细胞受体小鼠模型; 2）我们正在研究与自身免疫相关的多组重症肌无力相关基因，以建立自身免疫的遗传决定因素; 3）免疫性血小板减少性紫癜的抗原特异性治疗研究正在进行中。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。这些研究应该对自身免疫性疾病的发病机制和治疗产生重要的新见解，这是美国特别是职业女性中普遍存在的健康问题。

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 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 of immune thrombocytopenic purpura. 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.