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，我们想要确定导致自身免疫性疾病的T细胞的致病作用和抗原特异性，如多发性硬化症、凝血因子抑制、胰岛素依赖型糖尿病等。其次，我们希望确定特定抗原诱导的细胞凋亡作为治疗此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)我们重新启动了含有可能与多发性硬化症有关的抗原的重组分子的研究，目的是建立一项合作研究协议，在临床试验中测试这种形式的治疗。2)我们正在研究一组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；以及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注射因子VIII后形成封闭抗体。我们还将启动一种新的自身免疫性甲状腺炎转基因小鼠模型的研究。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。这些研究应该会对自身免疫性疾病的发病机制和治疗产生重要的新见解，这种疾病在美国是一个普遍的健康问题，特别是在职业女性中。 我们已经证明，可以为自身免疫性疾病重症肌无力建立转基因小鼠模型。这种疾病是由于一种抗体导致肌肉损伤，我们想测试针对T细胞的免疫耐受是否会影响这种疾病。我们已经发现，有许多因素影响抗原特异性疾病的诱导，我们计划使用我们的新小鼠品系来表征导致自身免疫症状的因素。

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, clotting factor inhibition, 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 reinitiated studies of recombinant molecules containing antigens potentially involved in multiple sclerosis with the goal of establishing a Cooperative research agreement to test such a form of therapy in a clinical trial. 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. We will also be initiating studies of a new transgenic mouse model for autoimmune thyroiditis. 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. We have shown that a transgenic mouse model can be constructed for the autoimmune disease myasthenia gravis. This disease is due to an antibody that causes muscle damage and we would like to test whether immunological tolerance directed at T cells can influence this disease. We have found that there are a number of factors that influence antigen-specific disease induction and we plan to use our new mouse strain to characterize the factors that precipitate the autoimmune symptoms.