| A Mimic of Viral Double-Stranded RNA Triggers Fulminant Type 1 Diabetes-like Syndrome in Regulatory T Cell-Deficient Autoimmune Diabetic Mouse. | |
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MedLine Citation:
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PMID: 21967896 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Ai Tada; Akira Shimada; Taketo Yamada; Yoichi Oikawa; Yoshifumi Yamada; Yoshiaki Okubo; Junichiro Irie; Jeffrey A Bluestone; Hiroshi Itoh |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-3 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: - ISSN: 1550-6606 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-4 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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