Autoimmune diabetes results from genetic defects manifest by antigen presenting cells.
In most cases, insulin-dependent diabetes results from autoimmune elimination of pancreatic beta cells by T lymphocytes that are generated as a result of complex polygenic interactions between particular MHC haplotypes and non-MHC linked susceptibility modifiers. Immature T cells with potential autoreactivity are normally destroyed in the thymus when they are highly activated after ligation of the T cell receptor (TCR) with "self" peptides bound to MHC molecules on antigen presenting cells (APC) such as macrophages. Here the hypothesis is put forth that non-MHC linked diabetes susceptibility genes contribute to subtle defects in the maturation of macrophages, and in synergy with a diabetogenic MHC haplotype generate APC that are unable to trigger autoreactive T cells to an activation state high enough to induce their destruction.
Serreze
D V
DV
Jackson Laboratory, Bar Harbor, Maine 04609.
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology*; D001327:Autoimmune Diseases / Q000209:etiology* / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000235:genetics; D006183:H-2 Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D013601:T-Lymphocytes / Q000276:immunology*
D006183:H-2 Antigens