Differentiation Inhibition of Regulatory T Cells in Hirosaki Hairless Rat Due to Deletion of The LY49 Family Genes Expressed in Thymic T Cells and Dendritic Cells
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概要
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he Hirosaki hairless rat （HHR） is a mutant strain derived from the Sprague-Dawley rat （SDR）. The HHR thymus was markedly small and showed underdeveloped medulla. In the HHR thymus, CD4 levels were decreased, suggesting that differentiation of CD4-positive T cells is disturbed. Because naturally occurring regulatory T （nTreg） cells complete the differentiation in the thymus, the maturation status of the cells was examined in the HHR thymus. Real-time PCR revealed reduced expression of the Foxp3 and CD25 （IL-2Rα） genes, important for nTreg differentiation, and flow cytometric analysis showed decreased number of CD4+CD25+Foxp3+nTreg cells, indicating that mature nTreg formation is repressed. To explore genes responsible for the failure of nTreg differentiation, comparative genome hybridization array was performed using DNA from HHR and SDR. This analysis identified two regions deleted on HHR chromosome 4. One region contained the Klra17 （similar to Ly49si1） gene and the other the Ly49s3, Ly49s4, Ly49i3 and Ly49i4 genes. RT-PCR of T cells and dendritic cells（ DCs）isolated from the SDR thymus revealed that the Klra17 gene was expressed in CD4-single positive （CD4-SP） cells and the Ly49s3 gene in DCs, indicating that HHR loses expression of the Klra17 and Ly49s3 genes in thymic CD4-SP cells and DCs, respectively. The mixed culture of CD4-SP cells and DCs from the HHR thymus exhibited poor nTreg differentiation. Taken together, these results suggest that the Klra17 and Ly49s3 genes are responsible for the differentiation of nTreg cells.
- 2013-00-00
著者
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Nanashima Naoki
Department of Biochemistry and Genome Biology, Hirosaki University Graduate School of Medicine
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Shimizu Takeshi
Department Of Biochemistry And Genome Biology Hirosaki University Graduate School Of Medicine
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Nanashima Naoki
Department Of Biochemistry And Genome Biology Hirosaki University Graduate School Of Medicine
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Tsuchida Shigeki
Department Of Biochemistry And Genome Biology Hirosaki University Graduate School Of Medicine
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Yamada Toshiyuki
Department Of Applied Physics Faculty Of Engineering University Of Tokyo:(present Address) Sony Corp
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Yamada Toshiyuki
Department of Biochemistry and Genome Biology, Hirosaki University Graduate School of Medicine
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