AUTOIMMUNE DIABETES RESULTS FROM GENETIC-DEFECTS MANIFEST BY ANTIGEN-PRESENTING CELLS

In most cases, insulin-dependent diabetes results from autoimmune elim ination of pancreatic beta cells by T lymphocytes that are generated a s a result of complex polygenic interactions between particular MHC ha plotypes and non-MHC linked susceptibility modifiers. Immature T cells with potential autoreactivity are normally destroyed in the thymus wh en they are highly activated after ligation of the T cell receptor (TC R) with ''self'' peptides bound to MHC molecules on antigen presenting cells (APC) such as macrophages. Here the hypothesis is put forth tha t non-MHC linked diabetes susceptibility genes contribute to subtle de fects in the maturation of macrophages, and in synergy with a diabetog enic MHC haplotype generate APC that are unable to trigger autoreactiv e T cells to an activation state high enough to induce their destructi on.