Immunization with streptozotocin-treated NOD mouse islets inhibits the onset of autoimmune diabetes in NOD mice

Abstract

In this study, we determined whether a single intraperitoneal injection of NOD islets exposed to streptozotocin (STZ; 5 mmol/l) in vitro could prevent onset of diabetes in female NOD mice. Pre-diabetic female NOD mice were injected with saline or islets exposed to either STZ or citrate buffer alone. Single injection of STZ-exposed islets significantly ( P<0.03) decreased the incidence of diabetes in pre-diabetic NOD mice compared to control groups. At 40 weeks of age, the onset of diabetes in NOD mice injected with STZ-treated islets was 16% (3/19) compared to 88% (14/16) in mice that received islets exposed to citrate buffer and 84% (26/31) in those mice injected with saline. Histological examination of the pancreases from normoglycemic mice given STZ-treated islets revealed numerous intact islets devoid of mononuclear cell infiltration while pancreases from control groups contained few intact islets infiltrated with mononuclear cells. This study demonstrates that immunization of pre-diabetic female NOD mice with syngeneic islets exposed to STZ prevents insulitis and onset of autoimmune diabetes. Our data suggest that exposure of islets to STZ may possibly induce the release of soluble antigens and/or cause an antigenic change in pancreatic β cells that subsequently results in immunization of pre-diabetic NOD mice.