The hsp60 peptide p277 arrests the autoimmune diabetes induced by the toxin streptozotocin.
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.
Elias
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Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Cohen
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IR
D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000145:classification; D018834:Chaperonin 60 / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000517:prevention & control*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005968:Glutamate Decarboxylase / Q000276:immunology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000145:classification; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000627:therapeutic use*; D013311:Streptozocin / Q000633:toxicity; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors
D001323:Autoantibodies; D018834:Chaperonin 60; D007004:Hypoglycemic Agents; D007074:Immunoglobulin G; D010446:Peptide Fragments; D013311:Streptozocin; D005968:Glutamate Decarboxylase