DECREASED IL-2 SYNTHESIS IN TYPE I DIABETES

I 型糖尿病中 IL-2 合成减少

• 批准号: 3145570
• 负责人: KAREN S ZIER
• 金额: $ 16.61万
• 依托单位: MOUNT SINAI SCHOOL OF MEDICINE OF CUNY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-05-01 至 1993-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3145570
• 关键词: T cell receptor; T lymphocyte; autoimmune disorder; biological signal transduction; densitometry; gene expression; genetic transcription; human subject; in situ hybridization; insulin dependent diabetes mellitus; interleukin 2; interleukin 4; interleukin 6; leukocyte activation /transformation; messenger RNA; molecular pathology; protein biosynthesis; siblings

The immune system is designed to recognize foreign invaders and to eliminate them from the body. Upon occasion, however, this mechanism can turn against itself and initiate and attack against shelf components leading to an autoimmune disease. Insulin dependent diabetes (IDD) is one autoimmune disease directed against the insulin producing beta cells. The working hypothesis of this study is that the abnormality in IL-2 levels may lead to aberrant effector responses mediated by T cells. the long-term goal of this proposal is to increase knowledge of the immunological abnormalities associated with IDD by defining the mechanism(s) underlying one of them, the deficiency in Interleukin-2 (IL-2) synthesis observed in IDDs. This phenomenon was first reported by us and has subsequently been confirmed by other investigators. It is one of few immunological defects affecting T cell function on a non-clonal level. In this resubmission, we will include non-diabetic, HLA-identical sibs of our patients in the research plan, in order to study whether any of the abnormalities associated with this defect may precede the onset of frank disease. The primary aim of the study is to test the hypothesis that IL-2 defect is regulated at the level of the expression of the IL-2 gene. In addition, we will examine whether signalling independent of the T cell receptor results in normal IL-2 synthesis and whether there are inhibitory lymphokines which prevent the IL-2 from stimulating T cell growth. The work described, largely based upon techniques of molecular biology, will build upon our earlier studies which used exclusively cellular techniques. Recent data have shown that Cyclosporin A can induce remission in newly diagnosed IDDs. The demonstration that the autoimmune process can be interrupted makes an understanding of the pathogenesis of IDD all the more important, since it may suggest additional therapeutic modalities. The elucidation of the IL-2 defect may lead to the development of such approaches, by precisely defining the level of control resulting in abnormalities of the cell medited immune system.

免疫系统旨在识别外国入侵者和 从身体中消除它们。 但是，有时这种机制可以 反对自己，对货架组件发起和攻击 导致自身免疫性疾病。 胰岛素依赖糖尿病（IDD）是一个 针对产生β细胞的胰岛素的自身免疫性疾病。 这 这项研究的工作假设是IL-2水平的异常可能 导致T细胞介导的异常效应子反应。 长期 该建议的目标是增加对免疫学的知识 通过定义基本机制与IDD相关的异常 其中之一，在介绍中观察到的白介素2（IL-2）合成的缺陷 IDD。 这种现象最初是由我们报道的，随后是 由其他调查人员确认。 这是少数免疫缺陷之一 在非共旋转水平上影响T细胞功能。 在此重新提交中，我们 将包括我们患者的非糖尿病的HLA，同一同胞 研究计划，以研究是否有任何异常 与此缺陷相关的可能是弗兰克病的发作。 这 该研究的主要目的是检验IL-2缺陷是 在IL-2基因的表达水平上调节。 另外，我们 将检查信号是否与T细胞受体结果无关 在正常的IL-2合成中，以及是否有抑制性淋巴细胞因素 防止IL-2刺激T细胞生长。 描述的工作， 很大程度上基于分子生物学技术，将基于我们的 早期使用专门使用细胞技术的研究。 最新数据 已经表明，环孢菌素A可以在新诊断的IDD中诱导缓解。 自身免疫过程可以中断的演示使 对IDD的发病机理的理解更为重要，因为它 可能暗示其他治疗方式。 IL-2的阐明 缺陷可能会通过精确地导致这种方法的发展 定义控制水平，导致细胞异常 冥想的免疫系统。