T cell-driven initiation and propagation of autoimmune diabetes

The destruction of beta cells in type 1 diabetes in humans and in autoimmune diabetes in the NOD mouse model is a consequence of chronic islet inflammation in the pancreas. The T cell-driven autoimmune response is initiated by environmental triggers which are influenced by the state of intestinal homeostasis and the microbiota. The disease process can be separated into two phases: firstly, initiation of mild, controlled, long-term infiltration and secondly, propagation of invasive inflammation which quickly progresses to beta cell deletion and autoimmune diabetes. In this review, we will discuss the cellular and molecular triggers that might be required for these two phases in the context of other issues including the unique anatomical location of pancreas, the location of T cell priming, the requirements for islet entry, and the events that ultimately drive beta cell destruction and the onset of diabetes.