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M9550884.TXT
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1995-03-25
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Document 0884
DOCN M9550884
TI Insulin immunization of nonobese diabetic mice induces a protective
insulitis characterized by diminished intraislet interferon-gamma
transcription.
DT 9505
AU Muir A; Peck A; Clare-Salzler M; Song YH; Cornelius J; Luchetta R;
Krischer J; Maclaren N; Department of Pathology and Laboratory Medicine,
University of; Florida, College of Medicine, Gainesville 32610.
SO J Clin Invest. 1995 Feb;95(2):628-34. Unique Identifier : AIDSLINE
MED/95164693
AB 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.
DE Animal Antibodies, Monoclonal CD4-Positive T-Lymphocytes/DRUG
EFFECTS/IMMUNOLOGY CD8-Positive T-Lymphocytes/DRUG EFFECTS/IMMUNOLOGY
Diabetes Mellitus, Insulin-Dependent/*IMMUNOLOGY/PREVENTION & CONTROL
Female Flow Cytometry Gene Expression/DRUG EFFECTS Immunization
Insulin/*IMMUNOLOGY Interferon Type II/*BIOSYNTHESIS Islets of
Langerhans/DRUG EFFECTS/*IMMUNOLOGY Lymphocyte Depletion
Macromolecular Systems Mice Mice, Inbred NOD Pancreatic
Diseases/CHEMICALLY INDUCED/*IMMUNOLOGY Support, Non-U.S. Gov't
Support, U.S. Gov't, P.H.S. Swine Transcription, Genetic/*DRUG EFFECTS
JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).