A mimic of viral double-stranded RNA triggers fulminant type 1 diabetes-like syndrome in regulatory T cell-deficient autoimmune diabetic mouse

Ai Tada, Akira Shimada, Taketo Yamada, Yoichi Oikawa, Yoshifumi Yamada, Yoshiaki Okubo, Junichiro Irie, Jeffrey A. Bluestone, Hiroshi Itoh

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 a 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.

Original languageEnglish
Pages (from-to)4947-4953
Number of pages7
JournalJournal of Immunology
Volume187
Issue number10
DOIs
Publication statusPublished - 2011 Nov 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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