Prevention of diabetes in the NOD mouse by a Th1 clone specific for a hsp60 peptide

Peptide-based therapies have been shown to be effective in the prevention o f diabetes in the NOD mouse. We have been interested in the T cell response elicited by such therapies and have been studying a T cell clone (C3.5) sp ecific for hs60 AA 437-460, generated following immunization with the hsp60 437-460 peptide. The C3.5 clone was CD4(+), V beta 8.3 TCR+, I-A(g7) restr icted and of the Th1 type. The injection of this clone into prediabetic NOD mice prevented the adoptive transfer of the disease and suppressed the dev elopment of spontaneous diabetes. This effect was reflected in a reduction in the degree and severity of insulitis in mice injected with this clone. I n addition, an antibody response was elicited to the C3.5 clone in mice giv en multiple injections of the clone. The epitope recognized by C3.5 is loca ted in the N-terminus of the hsp60 AA 437-460 peptide, and this clone was u nable to recognize the native hsp60 molecule. These data raise questions co ncerning the mechanism by which peptide-based therapies prevent autoimmune disease. (C) 2000 Academic Press.