EFFECT OF INTRATHYMIC ADMINISTRATION OF MYCOBACTERIAL HEAT-SHOCK-PROTEIN-65 AND PEPTIDE P277 ON THE DEVELOPMENT OF DIABETES IN NOD MICE - CAUTION REQUIRED IN VACCINATION STUDIES

Heat shock protein 65 (hsp65) and a derived peptide, p277, are autoant igens reported in IDDM. I.p. injection of hsp65 reduced diabetes incid ence in NOD mice and administration of p277 cured already diabetic mic e. Also, intrathymic (i.t.) administration of whole islets or GAD65 pr evented diabetes in NOD mice. The aim of this study was to evaluate wh ether i.t. injection of mycobacterial hsp65 or p277 can prevent diabet es in NOD mice. Three-week-old NOD female mice were injected intrathym ically with 50 mu g of hsp65 (n = 30), 5 mu g of p277 (n = 30), and PB S (n = 29). Diabetes incidence was observed for the following 300 days . Pancreas was then used for histological and immunohistological evalu ation. No significant differences in diabetes incidence were observed among the three groups of mice. Interestingly, hsp65-treated mice deve loped diabetes slightly faster at 177 +/- 6 days compared to 202 +/- 8 days (p = 0.015) for the p277-treated group and 197 +/- 7 days (p = 0 .033) for controls. The insulitis score and average islet size did not differ significantly among the three groups Of diabetic mice. Scatter ed TCR-gamma/delta positive cells were found in the pancreas of all gr oups of mice. In contrast, a huge infiltrate of TCR-gamma/delta positi ve cells was detected in four out of eight (50%) p277-diabetic NOD mic e. Thus, our data show an earlier onset of diabetes in hsp65-treated m ice and no improvement in the incidence with either hsp65 or p277, sug gesting that hsp65 acts in a different way from what was reported with GAD65. Caution is advised in future vaccination studies as hsp65 pose s a potential danger.