The APC1 concept of type I diabetes

Type I diabetes appears to be a T cell dependent disease. T cell reactivity is regulated by antigen presenting cells (APCs). In animal models of type I diabetes, abnormal reactivity of APCs, in particular of macrophages, probably is responsible for the progression of islet inflammation from T helper type 2 dependent benign periinsulitis to T helper type I dependent destructive intrainsulitis. The functional state of APCs during preferential stimulation of Th1 reactivities (APC1 state) is characterized by the release of TNFalpha, IL-12 and/or IL-18. The bias towards APC1 reactivity has been found due to defective inhibition via IL-10 and PGE2.