Treatment of autoimmune diabetes and insulitis in NOD mice with heat shock protein 60 peptide p277.

Abstract:

:We recently showed that a peptide of the M(r) 60,000 heat shock protein molecule, designated peptide p277, is a target of T-cells in autoimmune diabetes in NOD mice. Indeed, the p277 peptide could be used as a therapeutic agent to arrest the autoimmune process even after it was far advanced. The present study was done to document the effects of p277 therapy on inflammation of the islets and on T-cell responsiveness to p277. Groups of female NOD mice of various ages up to 17 weeks were treated with a single inoculation of p277 given before or after the onset of overt hyperglycemia. We now report that fragments of p277 can affect diabetes but that optimal therapy requires the whole peptide. The positive response to p277 was dependent on administration of a threshold dose of peptide. Therapy was accompanied by the regression of intra-islet inflammation and the reappearance of histologically normal islets. Successful peptide therapy was associated with downregulation of T-cell immunity to p277. Adoptive transfer experiments demonstrated that the spleen cells of p277-treated mice were no longer diabetogenic and also could suppress the diabetogenic potential of cotransferred spleen cells of untreated female NOD mice. These results indicate that specific treatment of diabetes with a defined peptide can reprogram the autoimmune response.

journal_name

Diabetes

journal_title

Diabetes

authors

Elias D,Cohen IR

doi

10.2337/diab.44.9.1132

subject

Has Abstract

pub_date

1995-09-01 00:00:00

pages

1132-8

issue

9

eissn

0012-1797

issn

1939-327X

journal_volume

44

pub_type

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