[Current concept of the pathogenesis of autoimmune type 1 diabetes mellitus]

In type 1 diabetes, the beta cell is selectively destroyed by T lymphocytes in a genetically susceptible individual. Susceptible HLA-class II molecules which have low binding affinity with putative beta cell antigens may fail in induction of self-tolerance. beta cell-reactive T cells may expand and infiltrate around the islet (benign insulitis) by stimulation with environmental factors through molecular mimicry and/or beta cell antigens per se. Benign insulitis may develop to destructive insulitis under overexpression of Th1 cytokines, which may be affected by non-MHC genes. Immune interventions to shift a cytokine balance to Th2 dominance in the insulitis lesion may be most realistic approach to suppress development of type 1 diabetes after the induction of autoimmunity.