Autoimmune Destruction of Pancreatic b Cells

Type 1 diabetes results from the destruction of insulin-producing pancreatic b cells by a b cell–specific autoimmune process. b Cell autoantigens, macrophages, dendritic cells, B lymphocytes, and T lymphocytes have been shown to be involved in the pathogenesis of autoimmune diabetes. b Cell autoantigens are thought to be released from b cells by cellular turnover or damage and are processed and presented to T helper cells by antigen-presenting cells. Macrophages and dendritic cells are the first cell types to infiltrate the pancreatic islets. Naive CD4 T cells that circulate in the blood and lymphoid organs, including the pancreatic lymph nodes, may recognize major histocompatibility complex and b cell peptides presented by dendritic cells and macrophages in the islets. These CD4 T cells can be activated by interleukin (IL)-12 released frommacrophages and dendritic cells. While this process takes place, b cell antigen-specific CD8 T cells are activated by IL-2 produced by the activated TH1 CD4 +