| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Virus infection to pancreatic beta cells could be one of environmental factors for the development of diabetes due to dysfunction of pancreatic beta cells. We developed the new animal model for non-insulin dependent diabetes mellitus by infection of the NDK25 variant of encephalomyocarditis (EMC) virus. To study the roles of mature cellular immunity on the pathogenesis of this model, RAG-2 knockout (KO) mice were infected with the NDK25 variant of EMCV. The original strain, 129/SvEv mouse was used as control. Glucose intolerance was observed in RAG-2KO, but not in control. Histological study showed that the pancreatic islets were mildly destroyed and the virus genome was detected in the islets in RAG-2KO, whereas the pancreatic islets appeared normal in control. Secondly, to elucidate roles of each lymphocyte subset in this model, MHC class II deficient mice, MHC class I deficient mice, and B-cell deficient mice, were infected with the NDK25 of EMCV. No mice showed glucose intolerance, and histological study demonstrated normal appearance of pancreatic islets in these mice.
From these results, we conclude that mature cellular immunity play a protective role against viral infection on the pathogenesis of glucose intolerance, and, once infected, the destruction of pancreatic beta cells by EMCV depends on their own ability to destroy beta cells
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