TRANSGENIC RAT MODEL OF INFLAMMATORY BOWEL DISEASE

人类 I 类主要组织相容性抗原 HLA-B27 具有很强的 与一组称为风湿病的疾病有关 脊柱关节病。这些疾病在临床上有充分记录 与炎症性肠病（IBD）的关系，尽管其基础 这种关系还不太清楚。我们已经培育出转基因老鼠 表达 HLA-B27，并观察到它们开发出多系统 与疾病谱非常相似的疾病 存在于携带 HLA-B27 的人类中。 这其中最引人注目的一点是 转基因大鼠的疾病是慢性胃肠道炎症， 特别是在结肠中，但也涉及小肠和 胃。这个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，对其的了解已 过去由于缺乏忠实且方便的动物而受到阻碍 模型。该项目将研究 T 淋巴细胞在 B27 转基因大鼠炎症性肠病的发病机制。 初步数据表明，T 细胞对于启动 这种疾病。这些实验将旨在确定 致病 T 的表型、个体发育和抗原特异性 细胞。结果应该是有关免疫的具体信息 导致肠道炎症的反应，预计这会 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.