DECREASED IL-2 SYNTHESIS IN TYPE I DIABETES

I 型糖尿病中 IL-2 合成减少

• 批准号: 3145571
• 负责人: KAREN S ZIER
• 金额: $ 17.27万
• 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/3145571
• 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.

免疫系统的设计是为了识别外来入侵者， 将它们从身体中清除。 然而，在某些情况下，这种机制可以 反其道而行之，发起并攻击货架组件 导致自身免疫性疾病 胰岛素依赖型糖尿病（IDD）是一种 针对产生胰岛素的β细胞的自身免疫性疾病。 的 本研究的工作假设是，IL-2水平的异常可能 导致由T细胞介导的异常效应子应答。 长期 该提案的目的是增加免疫学知识， 通过定义与IDD相关的机制， 其中之一，在白细胞介素-2（IL-2）合成中观察到的缺陷， IDDs. 这一现象是我们首先报道的，随后被 其他调查人员证实。 它是少数几种免疫缺陷之一 在非克隆水平上影响T细胞功能。 在这次重新提交中，我们 将包括非糖尿病，HLA相同的同胞，我们的患者在 研究计划，以研究是否有任何异常， 与此缺陷相关的可能先于弗兰克病的发作。 的 本研究的主要目的是检验IL-2缺陷是 在IL-2基因的表达水平上受到调节。 另外我们 将研究信号传导是否独立于T细胞受体的结果， 在正常的IL-2合成中，是否存在抑制性淋巴因子， 阻止IL-2刺激T细胞生长。 所描述的工作， 主要基于分子生物学技术，将建立在我们的 早期的研究只使用细胞技术。 最近的数据 表明环孢菌素A可以诱导新诊断IDDs的缓解。 自体免疫过程可以被中断的证明， 了解IDD的发病机制更加重要，因为它 可能会建议其他的治疗方式。 IL-2的阐明 缺陷可能会导致这种方法的发展， 确定导致细胞异常的控制水平 介导的免疫系统。