DECREASED IL-2 SYNTHESIS IN TYPE I DIABETES

免疫系统的设计是为了识别外来入侵者并 把它们从身体里清除掉。然而，有时，这种机制可以 反其道而行之，对货架组件发起攻击 导致一种自身免疫性疾病。胰岛素依赖型糖尿病(IDD)是 针对产生胰岛素的β细胞的自身免疫性疾病。这个 本研究的工作假设是IL-2水平的异常可能 导致T细胞介导的异常效应反应。长期的 这项建议的目标是增加对免疫学的了解 通过对缺铁性贫血发病机制的界定，发现与缺碘相关的异常(S) 其中之一，白介素2(IL-2)合成缺陷观察到 IDDS。这一现象首先由我们报道，随后被 得到了其他调查人员的证实。这是为数不多的免疫缺陷之一。 在非克隆水平上影响T细胞功能。在这次重新提交中，我们 将包括我们患者的非糖尿病、人类白细胞抗原相合的同胞 研究计划，以研究是否有任何异常 与此缺陷相关的疾病可能先于弗兰克病的发病。这个 这项研究的主要目的是检验IL-2缺陷是 在IL-2基因表达水平上进行调节。此外，我们 将检查信号独立于T细胞受体是否会导致 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 早期的研究完全使用了细胞技术。最新数据 已经证明环孢素A可以诱导新诊断的IDDS的缓解。 证明自身免疫过程是可以被中断的 了解IDD的发病机制就变得更加重要，因为它 可能会建议采用其他治疗方法。白介素2的研究进展 缺陷可能会导致这种方法的发展，确切地说 定义导致细胞异常的控制级别 冥想的免疫系统。

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.