Fourth Annual Rachmiel Levine Diabetes and Obesity SymposiumAutoimmune Destruction of Pancreatic β CellsYoon, Ji-Won*; Jun, Hee-SookAuthor Information Rosalind Franklin Comprehensive Diabetes Center, Department of Pathology, Chicago Medical School, North Chicago, IL. *Address for correspondence: Rosalind Franklin Comprehensive Diabetes Center, Chicago Medical School, 3333 Green Bay Road, North Chicago, IL 60064. E-mail: [email protected] American Journal of Therapeutics: November-December 2005 - Volume 12 - Issue 6 - p 580-591 doi: 10.1097/01.mjt.0000178767.67857.63 Buy Metrics Abstract Type 1 diabetes results from the destruction of insulin-producing pancreatic β cells by a β cell-specific autoimmune process. β Cell autoantigens, macrophages, dendritic cells, B lymphocytes, and T lymphocytes have been shown to be involved in the pathogenesis of autoimmune diabetes. β Cell autoantigens are thought to be released from β 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 β cell peptides presented by dendritic cells and macrophages in the islets. These CD4+ T cells can be activated by interleukin (IL)-12 released from macrophages and dendritic cells. While this process takes place, β cell antigen-specific CD8+ T cells are activated by IL-2 produced by the activated TH1 CD4+ T cells, differentiate into cytotoxic T cells and are recruited into the pancreatic islets. These activated TH1 CD4+ T cells and CD8+ cytotoxic T cells are involved in the destruction of β cells. In addition, β cells can also be damaged by granzymes and perforin released from CD8+ cytotoxic T cells and by soluble mediators such as cytokines and reactive oxygen molecules released from activated macrophages in the islets. Thus, activated macrophages, TH1 CD4+ T cells, and β cell-cytotoxic CD8+ T cells act synergistically to destroy β cells, resulting in autoimmune type 1 diabetes. © 2005 Lippincott Williams & Wilkins, Inc.