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).