Autoimmune destruction of pancreatic beta cells.
Type 1 diabetes results from the destruction of insulin-producing pancreatic beta cells by a beta cell-specific autoimmune process. Beta cell autoantigens, macrophages, dendritic cells, B lymphocytes, and T lymphocytes have been shown to be involved in the pathogenesis of autoimmune diabetes. Beta cell autoantigens are thought to be released from beta 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 beta 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, beta 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 beta cells. In addition, beta 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 beta cell-cytotoxic CD8+ T cells act synergistically to destroy beta cells, resulting in autoimmune type 1 diabetes.
Yoon
Ji-Won
JW
Rosalind Franklin Comprehensive Diabetes Center, Department of Pathology, Chicago Medical School, North Chicago, IL 60064, USA. ji-won.yoon@rosalindfranklin.edu
Jun
Hee-Sook
HS
D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000473:pathology* / Q000502:physiology; D051379:Mice; D010641:Phenotype; D051381:Rats
D005968:Glutamate Decarboxylase