Epitopes described in "Induction and acceleration of insulitis/diabetes in mice with a viral mimic (polyinosinic-polycytidylic acid) and an insulin self-peptide."

Article Authors:Hiroaki Moriyama; Li Wen; Norio Abiru; Edwin Liu; Liping Yu; Dongmei Miao; Roberto Gianani; F Susan Wong; George S Eisenbarth
Article Title:Induction and acceleration of insulitis/diabetes in mice with a viral mimic (polyinosinic-polycytidylic acid) and an insulin self-peptide.
Reference Detail
Reference ID:1006870
Abstract:Polyinosinic-polycytidylic acid (PolyIC), a "mimic" of double-stranded viral RNA, can induce diabetes when administered to rats with RT1(u), and immunization of normal H-2(d) mice (e.g., BALB/c) with insulin B:9-23 peptide (but not H-2(b)) results in the rapid induction of insulin autoantibodies. Because a mouse model of PolyIC/antigen-induced diabetes is lacking, we sought to produce insulitis and diabetes with either PolyIC and/or B:9-23 peptide immunization. Simultaneous administration of PolyIC and B:9-23 peptide to BALB/c mice (but with neither alone) induced insulitis. CD4 T lymphocytes predominated within islets, and the mice did not progress to hyperglycemia. Islets with transgene-induced expression of the costimulatory B7-1 molecule have enhanced diabetes susceptibility. Diabetes was frequently induced in B7-1 transgenic mice with H-2(d) in contrast to H-2(b) mice after PolyIC administration. Disease induction was accelerated by adding B:9-23 immunization to PolyIC. These studies demonstrate that "normal" mice have autoreactive T lymphocytes able to rapidly target islets and insulin given appropriate MHC alleles and that a peripherally administered insulin peptide (an altered peptide ligand of which is in clinical trials) can enhance specific anti-islet autoimmunity. These first PolyIC/insulin-induced murine models should provide an important tool to study the pathogenesis of type 1 diabetes with experimental autoimmune diabetes.
Affiliations:Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, CO 80262, USA.
Reference Type:Literature
PubMed ID:11943868
Journal:Proc Natl Acad Sci U S A
Journal Volume:99
Article Pages:5539-44
Journal ISSN:0027-8424
Article Chemical List:Antigens, CD4;Antigens, CD8;Insulin;Peptides;Poly I-C;Glucagon
Article MeSH List:Alleles; Animals; Antigens, CD4(biosynthesis); Antigens, CD8(biosynthesis); CD4-Positive T-Lymphocytes(metabolism); Diabetes Mellitus, Experimental(virology); Diabetes Mellitus, Type 1(metabolism); Genotype; Glucagon(metabolism); Immunohistochemistry; Insulin(chemistry); Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Peptides(chemistry); Poly I-C(pharmacology); Time Factors
Curation Last Updated:2015-07-30 20:19:36