Vaccination with glutamic acid decarboxylase plasmid DNA protects mice from spontaneous autoimmune diabetes and B7/CD28 costimulation circumvents that protection

The nonobese diabetic (NOD) mouse develops spontaneous T-cell-dependent aut oimmune diabetes. We tested here whether vaccination of NOD mice with a pla smid DNA encoding glutamic acid decarboxylase (GAD), an initial target isle t antigen of autoimmune T cell repertoire, would modulate their diabetes. O ur results showed that vaccination of young or old female NOD mice with the GAD-plasmid DNA, but not control-plasmid DNA, effectively prevented their diabetes, demonstrating that GAD-plasmid DNA vaccination is quite effective in abrogating diabetes even after the development of insulitis. The preven tion of diabetes did not follow the induction of immunoregulatory Th2 cells but was dependent upon CD28/B7 costimulation. Our results suggest a potent ial for treating spontaneous autoimmune diabetes via DNA vaccination with p lasmids encoding self-Ag, (C) 2001 Academic Press.