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Research Article Free access | 10.1172/JCI117707

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

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

Department of Pathology and Laboratory Medicine, University of Florida, College of Medicine, Gainesville 32610.

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Department of Pathology and Laboratory Medicine, University of Florida, College of Medicine, Gainesville 32610.

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Department of Pathology and Laboratory Medicine, University of Florida, College of Medicine, Gainesville 32610.

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Department of Pathology and Laboratory Medicine, University of Florida, College of Medicine, Gainesville 32610.

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Department of Pathology and Laboratory Medicine, University of Florida, College of Medicine, Gainesville 32610.

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Department of Pathology and Laboratory Medicine, University of Florida, College of Medicine, Gainesville 32610.

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Department of Pathology and Laboratory Medicine, University of Florida, College of Medicine, Gainesville 32610.

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Department of Pathology and Laboratory Medicine, University of Florida, College of Medicine, Gainesville 32610.

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First published February 1, 1995 - More info

Published in Volume 95, Issue 2 on February 1, 1995
J Clin Invest. 1995;95(2):628–634. https://doi.org/10.1172/JCI117707.
© 1995 The American Society for Clinical Investigation
First published February 1, 1995 - Version history
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.

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