title: A mimic of viral double-stranded RNA triggers fulminant type 1 diabetes-like syndrome in regulatory T cell-deficient autoimmune diabetic mouse.
abstract: Human fulminant type 1 diabetes (FT1D) is an extremely aggressive disease. The delay of proper diagnosis results in high mortality. However, the pathophysiology of this disease remains unclear. We took advantage of CD28-deficient NOD (CD28(-/-) NOD) mice, which have limited numbers of regulatory T cells and develop aggressive autoimmune diabetes, to create a FT1D model that mimicked the disease in humans. Young CD28(-/-) NOD mice were injected with polyinosinic-polycytidylic acid to activate innate immunity in an effort to induce diabetes onset. In this model, innate immune cell activation precedes the onset of diabetes similar to ∼70% of FT1D patients. Eighty-three percent of CD28(-/-) NOD mice developed diabetes within 1-6 d after injection of polyinosinic-polycytidylic acid. Moreover, T cells infiltrated the pancreatic exocrine tissue and destroyed α cells, an observation characteristic of human FT1D. We conclude that an FT1D-like phenotype can be induced in the background of autoimmune diabetes by a mimic of viral dsRNA, and this model is useful for understanding human FT1D.
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Tada
authors.forename: Akira
authors.initials: A
authors.lastname: Shimada
authors.forename: Taketo
authors.initials: T
authors.lastname: Yamada
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Oikawa
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Yamada
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Okubo
authors.forename: Junichiro
authors.initials: J
authors.lastname: Irie
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bluestone
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D004770:Enterovirus / Q000235:genetics / Q000276:immunology; D005260:Female; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D018716:Molecular Mimicry / Q000235:genetics / Q000276:immunology*; D012330:RNA, Double-Stranded / Q000276:immunology*; D012367:RNA, Viral / Q000276:immunology*; D013577:Syndrome; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
chemical_list: D012330:RNA, Double-Stranded; D012367:RNA, Viral