Nfkbid Overexpression in Nonobese Diabetic Mice Elicits Complete Type 1 Diabetes Resistance in Part Associated with Enhanced Thymic Deletion of Pathogenic CD8 T Cells and Increased Numbers and Activity of Regulatory T Cells.
Type 1 diabetes (T1D) in both humans and NOD mice is caused by T cell-mediated autoimmune destruction of pancreatic β cells. Increased frequency or activity of autoreactive T cells and failures of regulatory T cells (Tregs) to control these pathogenic effectors have both been implicated in T1D etiology. Due to the expression of MHC class I molecules on β cells, CD8 T cells represent the ultimate effector population mediating T1D. Developing autoreactive CD8 T cells normally undergo extensive thymic negative selection, but this process is impaired in NOD mice and also likely T1D patients. Previous studies identified an allelic variant of