Type 1 diabetes (T1D) has devastating effects on the health and quality of life of those affected. Several studies have associated the proinflammatory cytokine IL‐18 with an increased risk of T1D. Significantly higher IL-18 cytokine levels are seen in individuals at high risk for developing disease, increased serum levels of IL‐18 have been observed in T1D, and the presence of multiple islet autoantibodies in new‐onset diabetics was found to be associated with increased serum levels of IL‐18. Furthermore, our recent investigations demonstrate a role for IL‐18 in expanding the pool of islet‐destructive T cells during pre‐diabetes. Taking the elevated serum levels of IL-18 in T1D and enhanced survival properties of IL-18 receptor (IL-18R)-expressing CD8 T cells into account, there might be a connecting link between IL-18R+ CD8 T cells and T1D pathogenesis. Hence, in the present study we propose that IL-18R+ CD8 T cells may underlie the direct or indirect islet destruction associated with T1D. Furthermore, IL-18 expression has been linked to the C-C chemokine receptor type 7 (CCR7). Specifically, IL-18 has been shown to induce expression of CCR7, and IL-18-activated cells can stimulate the production of the CCR7 ligand CCL19. Based on this data and our preliminary data showing an increase in proportion of a transitional CD4 T cell population expressing CCR7 in new-onset T1D patients, we postulate that the CCR7 ligands CCL19 and CCL21 will be overexpressed in the pancreas and spleen of T1D patients when compared to control, autoantibody positive, and T2D patients. Overall, the goal of our studies is to fully understand the role of IL-18R+ CD8 T cells and associated cytokines and soluble factors in T1D pathogenesis. With the aid of nPOD, human spleen and pancreatic tissue specimens will be utilized for immunohistochemical studies to determine islet infiltration of IL-18R+ CD8 T cells, as well as differential expression of cytokines and soluble factors important for the development of T1D.