Insulin immunization of nonobese diabetic mice induces a protective insulitis characterized by diminished intraislet interferon-gamma transcription.
We reported previously that daily injections of isophane insulin prevented both hyperglycemia and insulitis in nonobese diabetic (NOD) mice (Atkinson, M., N. Maclaren; and R. Luchetta. 1990. Diabetes. 39:933-937). The possible mechanisms responsible include reduced immunogenicity of pancreatic beta-cells from "beta-cell rest" and induced active immunoregulation to insulin (Aaen, IK., J. Rygaard, K. Josefsen, H. Petersen, C. H. Brogren, T. Horn, and K. Buschard. 1990. Diabetes. 39:697-701). We report here that intermittent immunizations with insulin or its metabolically inactive B-chain in incomplete Freund's adjuvant also prevent diabetes in NOD mice, whereas immunizations with A-chain insulin or with BSA do not. Adoptive transfer of splenocytes from B-chain insulin-immunized mice prevented diabetes in recipients co-infused with diabetogenic spleen cells, an effect that was abolished by prior in vivo elimination of either CD4+ or CD8+ cells. Insulin immunization did not reduce the extent of intraislet inflammation (insulitis); however, it did abolish expression of IFN-gamma mRNA within the insulitis lesions. Immunizations with insulin thus induce an active suppressive response to determinants on the B-chain that converts the insulitis lesion from one that is destructive to one that is protective.
Muir
A
A
Department of Pathology and Laboratory Medicine, University of Florida, College of Medicine, Gainesville 32610.
Peck
A
A
Clare-Salzler
M
M
Song
Y H
YH
Cornelius
J
J
Luchetta
R
R
Krischer
J
J
Maclaren
N
N
D000818:Animals; D000911:Antibodies, Monoclonal; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D007114:Immunization; D007328:Insulin / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis*; D007515:Islets of Langerhans / Q000187:drug effects / Q000276:immunology*; D008212:Lymphocyte Depletion; D046911:Macromolecular Substances; D051379:Mice; D016688:Mice, Inbred NOD; D010182:Pancreatic Diseases / Q000139:chemically induced / Q000276:immunology*; D013552:Swine; D014158:Transcription, Genetic / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D007328:Insulin; D046911:Macromolecular Substances; D007371:Interferon-gamma