期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：8
页码：5539-5544
DOI：10.1073/pnas.082120099
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Polyinosinic-polycytidylic acid (PolyIC), a "mimic" of double-stranded viral RNA, can induce diabetes when administered to rats with RT1u, and immunization of normal H-2d mice (e.g., BALB/c) with insulin B:9-23 peptide (but not H-2b) 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-2d in contrast to H-2b 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.
