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 immunizing female BALB/c, C57B1/6, National Marine Research Institute (NMRI) and non-obese diabetic (NOD) mice once or twice with glumatic acid decarboxylase, GAD65, bovine serum albumin, or phosphate-buffered saline in incomplete Freunds adjuvant, or not treating. Mice immunized with GAD65, showed splinic T-cell reactivity to GAD 65 in vitro assessed by cytokine secretion. However untreated NOD mice did not. NOD mice showed a vigorous IFN-gamma response after one immunization, whereas NMRI mice 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, compared to C57B1/6 mice. High levels of GAD65 antibodies were detected in all mice immunized with GAD65, though lower levels were found in C57B1/6 mice. Histological analysis of pancreata revealed that no control mice, regardless of treatment, had mononuclear cell infiltration in the islets. In NOD mice, peri-insulitis was detected in all groups, but less so in GAD65 and bovine serum albumin (BSA) immunized animals. These data demonstrate that NOD mice respond more vigorously to immunization 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.
Plesner
A
A
Hagedorn Research Institute, Gentofte, DK-2820, Denmark.
Worsaae
A
A
Dyrberg
T
T
Gotfredsen
C
C
Michelsen
B K
BK
Petersen
J S
JS
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D000917:Antibody Formation / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced* / Q000276:immunology* / Q000473:pathology; D004198:Disease Susceptibility; D005260:Female; D005620:Freund's Adjuvant / Q000276:immunology / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D007114:Immunization; D007515:Islets of Langerhans / Q000187:drug effects* / Q000473:pathology*; D007527:Isoenzymes / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D012710:Serum Albumin, Bovine / Q000276:immunology / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000906:Antibodies; D007527:Isoenzymes; D012710:Serum Albumin, Bovine; D005620:Freund's Adjuvant; D005968:Glutamate Decarboxylase