IMMUNIZATION OF DIABETES-PRONE OR NON-DIABETES-PRONE MICE WITH GAD65 DOES NOT INDUCE DIABETES OR ISLET-CELL PATHOLOGY

Glutamic acid decarboxylase autoimmunity was investigated by immunizin g female BALB/c, C57Bl/6, National Marine Research Institute (NMRI) an d non-obese diabetic (NOD) mice once or twice with glumatic acid decar boxylase, GAD65, bovine serum albumin, or phosphate-buffered saline in incomplete Freunds adjuvant, or not treating. Mice immunized with GAD 65, showed splinic T-cell reactivity to GAD 65 in vitro assessed by cy tokine secretion. However untreated NOD mice did not. NOD mice showed a vigorous IFN-gamma response after one immunization, whereas NMRI mic e showed a lower response. IL-4 and IL-10 were only detected after two immunizations with higher levels in BALB/c, NMRI and NOD mice, compar ed to C57Bl/6 mice. High levels of GAD65 antibodies were detected in a ll mice immunized with GAD65, though lower levels were found in C57Bl/ 6 mice. Histological analysis of pancreata revealed that no control mi ce, regardless of treatment, had mononuclear cell infiltration in the islets. In NOD mice, peri-insulitis was detected in all groups, but le ss so in GAD65 and bovine serum albumin (BSA) immunized animals. These data demonstrate that NOD mice respond more vigorously to immunizatio n with GAD65 than non-diabetic mice strains. Furthermore, immunization with GAD65 is not sufficient to provoke onset of diabetes in NOD mice or induce islet cell pathology in non-diabetes prone mice, (C) 1998 A cademic Press.