TRANSGENIC RAT MODEL OF INFLAMMATORY BOWEL DISEASE

人类I类主要组织相容性抗原人类白细胞抗原-B27强烈 与一组风湿性疾病有关，称为 脊椎关节病。这些疾病在临床上有很好的记录。 与炎症性肠病(IBD)的关系，尽管 这种关系还没有得到很好的理解。我们已经培育出转基因大鼠 表达了人类白细胞抗原B27，并观察到它们形成了一个多系统 与疾病谱系有很大相似之处的疾病 在携带人类白细胞抗原-B27的人类中遇到。其中最引人注目的是 转基因大鼠的疾病是慢性胃肠道炎症， 尤其是在结肠，但也累及小肠和 胃。这一过程与人类有许多共同的重要特征 IBD，因此，B27转基因大鼠需要被视为 IBD的潜在重要动物模型，对其了解有 过去因为缺乏忠诚和方便的动物而受到阻碍 模特。本项目将研究T淋巴细胞在人类免疫缺陷病毒感染中的作用。 B27转基因大鼠炎症性肠病发病机制的研究 初步数据表明，T细胞是启动 这种疾病。这些实验将被用来识别 致病T细胞的表型、个体发育和抗原特异性 细胞。结果应该是关于免疫的特定信息 导致肠道炎症的反应，这预计会 直接导致从根本上提高对 IBD的发病机制。

The human class I major histocompatibility antigen HLA-B27 is strongly associated with a group of rheumatic disorders termed spondyloarthropathies. These disorders show a clinically well documented relationship to inflammatory bowel disease (IBD), although the basis for this relationship is not well understood. We have produced transgenic rats expressing HLA-B27, and have observed that they develop a multisystem disease that bears strong resemblance to the spectrum of disease encountered in humans with HLA-B27. The most striking aspect of this disease in the transgenic rats is chronic gastrointestinal inflammation, particularly in the colon but also involving the small intestine and stomach. This process shares a number of significant features with human IBD, and as a result, the B27 transgenic rats need to be considered as a potentially important animal model for IBD, understanding of which has been hampered in the past for lack of a faithful and convenient animal model. This project will examine the role of T lymphocytes in the pathogenesis of the inflammatory bowel disease of the B27 transgenic rats. Preliminary data indicates that T cells are critical for the initiation of the disease. These experiments, will be directed toward identifying the phenotype, ontogeny, and antigenic specificity of the disease-inducing T cells. The results should be specific information regarding the immune response leading to intestinal inflammation, and this would be expected to lead directly to a fundamentally improved understanding of the pathogenesis of IBD.