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a Rosalind Franklin Comprehensive Diabetes Center, Chicago Medical School, North Chicago, Illinois 60064, USA
Key Words: type 1 diabetes • Kilham rat virus • encephalomyocarditis virus • macrophages • T cells • cytokines • pancreatic  cells
Address for correspondence: Hee-Sook Jun, Rosalind Franklin Comprehensive Diabetes Center, Chicago Medical School, North Chicago, IL 60064. Voice: 847-578-8341; fax: 847-578-3432. e-mail: hee-sook.jeon{at}rosalindfranklin.edu
More than 10 viruses have been reported to be associated with the development of type 1 diabetes-like symptoms in animals, with the best evidence coming from studies on the D variant of encephalomyocarditis (EMC-D) virus in mice and Kilham rat virus (KRV) in rats. A high titer of EMC-D viral infection results in the development of diabetes within 3 days, primarily due to the rapid destruction of
cells by viral replication within the cells. A low titer of EMC-D viral infection results in the recruitment of macrophages to the islets. Soluble mediators produced by activated macrophages play a critical role in the destruction of residual cells. A single amino acid at position 776 of the EMC viral genome controls the diabetogenicity of the virus. In contrast, KRV causes autoimmune type 1 diabetes in diabetes-resistant BioBreeding (DR-BB) rats without direct infection of cells. Macrophages play an important role in the development of diabetes in KRV-infected DR-BB rats. As well, KRV infection preferentially activates effector T cells, such as Th1-like CD45RC+CD4+ T cells and CD8+ T cells, and downregulates regulatory T cells, such as Th2-like CD45RC–CD4+ T cells. This results in the breakdown of the immune balance, contributing to the development of diabetes in KRV-infected DR-BB rats.
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