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PMID: 7860747 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Insulin immunization of nonobese diabetic mice induces a protective insulitis characterized by diminished intraislet interferon-gamma transcription.

The Journal of clinical investigation ·Vol. 95 ·No. 2 ·1995-02-00 ·Pages 628-34

Muir A, Peck A, Clare-Salzler M, Song YH, Cornelius J, Luchetta R, Krischer J, Maclaren N

Abstract

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.

MeSH Terms
Animals Antibodies, Monoclonal CD4-Positive T-Lymphocytes/drug effects,immunology CD8-Positive T-Lymphocytes/drug effects,immunology Diabetes Mellitus, Type 1/immunology,prevention & control Female Flow Cytometry Gene Expression/drug effects Immunization Insulin/immunology Interferon-gamma/biosynthesis Islets of Langerhans/drug effects,immunology Lymphocyte Depletion Macromolecular Substances Mice Mice, Inbred NOD Pancreatic Diseases/chemically induced,immunology Swine Transcription, Genetic/drug effects
Chemicals
Antibodies, Monoclonal Insulin Macromolecular Substances Interferon-gamma
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Muir A
Department of Pathology and Laboratory Medicine, University of Florida, College of Medicine, Gainesville 32610.
Peck A
Clare-Salzler M
Song Y H
Cornelius J
Luchetta R
Krischer J
Maclaren N
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI117707
Published
1995-02-00
Pages
628-34
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC295528
Subset
IM
Grants
NICHD NIH HHS · R01 HD19469-09 · United States
External Links
PubMed source DOI: 10.1172/JCI117707 PMC Full Text View journal details
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