Effects of vaccination with heat shock proteins on streptozotocin induced diabetes in histidine decarboxylase knockout mice

Abstract

Type 1 diabetes mellitus (T1D) is an immune mediated disease in which heat shock proteins (hsps) may be involved in the development of the disease. Furthermore, vaccination with different hsps prevented the development of multiple low-dose streptozotocin (STZ) induced autoimmune diabetes in C57BL/KSJ mice. Histamine influences many aspects of the immune response, including Th1/Th2 balance and antibody production. Therefore, a study of diabetes-related immune processes was considered of interest in histidine decarboxylase knockout (HDC-KO) mice. The aim of our study was i) to characterize antibody production in response to vaccination with p277 or hsp65 in wild type (WT) BALB/c and HDC-KO mice, and ii) to establish a possible correlation between vaccination and the changes in the pattern of STZ diabetes. An ELISA was employed to measure the hsp65- and p277-specific antibody levels. To induce diabetes multiple low-dose of STZ was used. Vaccination with p277 and hsp65 altered the pattern of STZ diabetes both in HDC-KO and WT animals, characterized by a transient increase followed by sustained reduction of blood sugar levels as compared to controls. However, vaccination with hsp65 and p277 caused a significant anti-p277 and anti-hsp65 antibody level increase only in WT animals. Multiple low-doses of STZ were able to induce diabetes in HDC-KO mice and the development of diabetes was prevented by vaccination with hsps. This protection developed in spite of the fact that vaccination caused a significant antibody level increase only in WT animals. To explain the therapeutic effect of vaccination we need further examination of the HDC KO strain.