| First Author | Moriyama H | Year | 2002 |
| Journal | Proc Natl Acad Sci U S A | Volume | 99 |
| Issue | 8 | Pages | 5539-44 |
| PubMed ID | 11943868 | Mgi Jnum | J:76064 |
| Mgi Id | MGI:2178494 | Doi | 10.1073/pnas.082120099 |
| Citation | Moriyama H, et al. (2002) Induction and acceleration of insulitis/diabetes in mice with a viral mimic (polyinosinic-polycytidylic acid) and an insulin self-peptide. Proc Natl Acad Sci U S A 99(8):5539-44 |
| abstractText | 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. |
