Disruption of T cell tolerance in type 1 diabetes

项目摘要/摘要 像1型糖尿病这样的自身免疫性疾病是由免疫耐受性崩溃引起的。我们现在有了 了解免疫耐受性是由一个多层网络组成的，它可以防止这种不适 回复正在检查中。在这项计划项目赠款中，三个互补的团队将共同努力 进一步揭示这些检查点是如何运作的，以提高我们对自身免疫的理解，并最终 提高其治疗水平。该计划项目将由三个高度协作和互动的项目牵头 由Mark Anderson博士(项目1)、Jeff Blustone博士(项目2)和John Kappler博士(项目3)以及两个 科学核心(动物核心和分子核心)。资助金的主要主题是： 1.中枢胸腺耐受对T1D患者T效应和Treg谱的影响 2.胰岛素是T1D中T效应细胞和T调节细胞的关键自身抗原特异性。 3.T1D中T调节细胞的多肽特异性 4.利用胰岛抗原的多肽结合特性，改进生物检测和耐受方法。 这项工作的长期目标是提高我们对T细胞耐受性是如何控制和 进一步提炼1型糖尿病患者自身反应性T细胞反应的特异性。调查人员将 在动物模型和患有1型糖尿病的人类受试者中使用最先进的工具。结果： 这些研究将有助于进一步加深我们对自身免疫的理解，并有助于改进其治疗方法。 治疗和诊断。

Project Summary/Abstract Autoimmune diseases like type 1 diabetes arise through a breakdown in immune tolerance. We have now come to understand that immune tolerance consists of a multi-layered network that keeps such untoward responses in check. In this program project grant, three complementary teams will be working together to further unravel how these checkpoints operate to improve our understanding of autoimmunity and ultimately improve its treatment. This program project will have three highly collaborative and interactive projects headed by Drs. Mark Anderson (Project 1), Jeff Bluestone (Project 2) and John Kappler (Project 3) along with two scientific cores (Animal core and Molecular core). The major themes of the grant are: 1. The impact of central thymic tolerance on the T effector and Treg repertoire in T1D.. 2. Insulin as a critical self-antigen specificity for both T effectors and T regulatory cells in T1D. 3. Peptide specificity of Tregulatory cells in T1D 4. Using peptide binding characteristics of islet antigens to improve bioassays and tolerance methods. The long term objectives of this work is to improve our understanding of how T cell tolerance is controlled and the further refining the specificity of the autoreactive T cell response in type 1 diabetes. The investigators will be using state of the art tools in both animal models and in human subjects with type 1 diabetes. Results of these studies will help further refine our understanding of autoimmunity and help improve methods for its treatment and diagnosis.