Cytokine receptor populations in human autoimmune diabetes

描述（由申请人提供）：1型糖尿病（T1D）是由针对产生胰岛素的胰岛细胞的自身免疫引起的，对健康和生活质量具有破坏性影响。在这个应用中，我们建议研究CD8 T细胞的一个重要的新亚群在新发糖尿病患者中的作用。该群体由IL-18受体（IL-18R）的表达定义，包含具有先天和效应特征的细胞。本应用的目的是了解这种il - 18r阳性CD8 T细胞的作用

DESCRIPTION (provided by applicant): Type 1 diabetes (T1D), which results from autoimmunity directed against insulin-producing islet cells, has devastating effects on health and quality of life. In this application we propose to investigate the role of an important new subpopulation of CD8 T cells in new-onset diabetes patients. This population is defined by expression of the IL-18 receptor (IL-18R) and contains cells with both innate and effector features. The goal of this application is to understand the role of this IL-18R-positive CD8 T cell subpopulation in human T1D. This work is important for several reasons. First, this expanded and unique T cell subpopulation has never been described in circulating leukocytes of new-onset human Type 1 diabetics. Second, IL-18 and its receptor are risk factors for autoimmune diseases, indicating that these factors may induce autoimmune reactions related to type 1 diabetes. Third, the IL-18 binding protein has been evaluated for its use in clinical trials for rheumatoid arthritis, and the work described here could provide the basis for clinical trials with the binding protein in diabetes patients. Fourth, the presence of this specific cell population could be developed as a surrogate marker for disease susceptibility and identify patients who would respond positively to treatment with the binding protein. Fifth, our results will provide critical "proof of concept" data on the activation and pathogenicity of this cell population in human diabetes. Sixth, these investigations will uncover the role of circulating factors that stimulate or inhibit the pathogenic potential of this cell population. Therefore, our approach will provide novel findings facilitating clinical trials blocking the IL-18R pathway in new-onset diabetes patients.