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

10 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

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Double-Stranded RNA
Viral RNA
Regulatory T-Lymphocytes
Type 1 Diabetes Mellitus
Inbred NOD Mouse
Poly I-C
Innate Immunity
Observation
T-Lymphocytes
Phenotype
Injections
Mortality

ASJC Scopus subject areas

  • Immunology

Cite this

A mimic of viral double-stranded RNA triggers fulminant type 1 diabetes-like syndrome in regulatory T cell-deficient autoimmune diabetic mouse. / Tada, Ai; Shimada, Akira; Yamada, Taketo; Oikawa, Yoichi; Yamada, Yoshifumi; Okubo, Yoshiaki; Irie, Junichiro; Bluestone, Jeffrey A.; Itoh, Hiroshi.

In: Journal of Immunology, Vol. 187, No. 10, 15.11.2011, p. 4947-4953.

Research output: Contribution to journalArticle

Tada, Ai ; Shimada, Akira ; Yamada, Taketo ; Oikawa, Yoichi ; Yamada, Yoshifumi ; Okubo, Yoshiaki ; Irie, Junichiro ; Bluestone, Jeffrey A. ; Itoh, Hiroshi. / A mimic of viral double-stranded RNA triggers fulminant type 1 diabetes-like syndrome in regulatory T cell-deficient autoimmune diabetic mouse. In: Journal of Immunology. 2011 ; Vol. 187, No. 10. pp. 4947-4953.
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