TRANSGENIC RAT MODEL OF INFLAMMATORY BOWEL DISEASE

人I类主要组织相容性抗原HLA-B27是一种强免疫原。 与一组风湿性疾病有关， 脊椎关节病这些疾病在临床上有充分的证据证明， 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老鼠 表达HLA-B27，并观察到他们开发了一个多系统， 与疾病谱有很大相似性的疾病 人类HLA-B27 最引人注目的是 转基因大鼠中的疾病是慢性胃肠道炎症， 特别是在结肠，但也涉及小肠， 胃这一过程与人类的许多重要特征相同， IBD，因此，B27转基因大鼠需要被视为 IBD的潜在重要动物模型，了解这一点， 在过去，由于缺乏忠实和方便的动物， 模型本项目将研究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细胞是启动免疫反应的关键。 这种疾病这些实验，将针对确定 表型、个体发育和抗原特异性的疾病诱导T 细胞结果应该是关于免疫的具体信息 反应导致肠道炎症，这将是预期的 直接导致从根本上改善对 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.