The development of
autoimmune diabetes in the NOD strain of mice (H-2g7) is marked by the presence of T-cells reactive to the p277
peptide of the 6O-kDa
heat shock protein (hsp60). We have found that the p277
peptide can be used as a therapeutic
vaccine to arrest NOD diabetes. Recently, we found that T-cell autoimmunity to p277 also develops spontaneously in C57BL/KsJ mice (H-2d) during the induction of
autoimmune diabetes by a very low dose of the beta-cell toxin
streptozotocin (STZ). We now report the inhibition of STZ toxin-induced
autoimmune diabetes by p277
peptide therapy. Administration of two doses each of 100 micrograms of
peptide p277 in
mineral oil given 1 week after toxin induction and 85 days later was most effective. The effect of p277 on STZ toxin-induced diabetes was marked by a shift in p277 autoimmunity from a T-cell proliferative response to the production of anti-p277
antibodies. The anti-p277
antibodies were predominantly of the
IgG1 and
IgG2b isotypes, known to be regulated by Th2 type
cytokines;
IgG2a antibody, known to be dependent on
interferon (IFN)-gamma, was induced to a much lesser degree.
Peptide p277
therapy was specific: treatment of the mice with an immunogenic
peptide from the sequence of another
antigen, GADp34, failed to prevent the development of diabetes. The GADp34
peptide induced lower titers of specific
antibodies, and the
antibodies were predominantly of the
IgG2a class. Thus, p277
peptide therapy, marked by the induction of Th2-type
antibodies, can be effective in toxin-induced
autoimmune diabetes.