IMMUNOREGULATION IN THE NOD MOUSE

描述(改编自申请人的摘要)：普遍持有的观点 自身免疫性疾病是指发病机制和疾病主要由一种 免疫系统的不平衡，特征是不能调节 免疫途径，尤其是那些导致组织破坏的途径。这个 非肥胖糖尿病(NOD)小鼠自发发生自身免疫性IDDM和IS 已知存在许多免疫调节缺陷。这样做的第一个目的是 提案的目的是通过 分析特定的免疫调节功能(抗原提呈、 黏附分子、细胞因子和趋化因子的表达) 抗糖尿病。在这个项目的第二个目标下，贡献 将对Th1和Th2T细胞的免疫调节作用进行研究。虽然 其他人已经证明，细胞因子水平的增加是由 调节性Th2 T细胞可导致NOD疾病的延迟或抑制 小鼠，目前还没有令人信服的证据表明Th2 T细胞在 预防。申请者正在从NOD中生产Th2T细胞系和克隆 从糖尿病耐受小鼠和NOD同源基因小鼠确定 保护性Th2 T细胞可以被分离出来，如果是这样的话，什么构成了 保护性表型。这些研究的结果应该会提供一个 更清楚地了解导致自身免疫性糖尿病和 纠正特异性免疫功能障碍是否会导致 疾病的预防或改善。

DESCRIPTION (adapted from applicant's abstract): A widely held view of autoimmune disease is that pathogenesis and disease result primarily from an imbalance in the immune system, characterized by a failure to regulate immunological pathways, particularly those causing tissue destruction. The non-obese diabetic (NOD) mouse spontaneously develops autoimmune IDDM and is known to have a number of immunoregulatory defects. The first aim of this proposal is to further delineate these defects or imbalances through the analysis of specific immunoregulatory functions (antigen presentation, expression of adhesion molecules, cytokine and chemokine production) in diabetes-resistant. Under the second aim of this project, the contribution of Th1 and Th2 T cells to immunoregulation will be investigated. Although it has been shown by others that increasing levels of cytokines made by regulatory Th2 T cells can lead to delay or inhibition of disease in the NOD mouse, there has been no convincing demonstration that Th2 T cells mediate prevention. The applicant is producing Th2 T cell lines and clones from NOD mice and from diabetes-resistant NOD congenic mice to determine whether protective Th2 T cells can be isolated and if so, what constitutes a protective phenotype. The results from these studies should provide a clearer understanding of factors that contribute to autoimmune diabetes and whether correction of specific immunological dysfunction will result in prevention or amelioration of disease.