Figure 3. The pathogenesis of islet cell destruction. Islet cell proteins are presented by antigen presenting cells (APCs) to naïve Th0 type CD4+ T cells in association with MHC class II molecules. Interleukin (IL)-12 is thus secreted by APCs that promotes the differentiation of Th0 cells to Th1 type cells. Th1 cells secrete IL-2 and IFN-γ that further stimulate CD8+ cytotoxic T cells or macrophages to release free radicals (super-oxides) or perforin/granzymes, leading to ß cell apoptosis or death. CD8+ cytotoxic T cells further mediate ß cell death by Fas mediated mechanisms. Interleukin (IL)-4, on the other hand, secreted mainly by natural killer T (NKT) cells drives Th0 cell to Th2 pathway leading to benign insulitis.