Are IL-18 receptor-bearing CD8 T cells pathogenic in human Type 1 diabetes?

Type1 diabetes has devastating effects on the health and quality of life of individuals with this condition. Despite excellent research, the environmental stimulus and cell population responsible for precipitating the disease is not known. Studies in animal models have provided critical insights on the disease process. However, detailed phenotypic analysis of effector populations in human diabetes has been comparably limited. For this application we have defined a population of CD8 T cells that is expanded in new onset diabetes patients. This population is defined by expression of the IL-18 receptor (IL-18R). The goal of this application is to understand the role of this T cell population in human Type 1 diabetes. This work is important for several reasons. First, the T cell population has never been described. Second, IL-18 is a risk factor for other autoimmune diseases such as celiac disease. Third, evaluation of the IL-18 binding protein for its use in clinical trials has been performed, and the work described here could provide the basis for clinical trials of the binding protein in diabetes patients. Fourth, IL-18R levels could be developed as a surrogate marker for disease susceptibility and identify patients who would respond to treatment with the binding protein. Therefore, our approach will provide proof of concept studies facilitating clinical trials blocking the IL-18R pathway in new onset diabetes patients.