| Project/Area Number |
16590413
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
NAKANO Naoko Tokyo University of Science, Research Institute for Biological Sciences, Associate professor, 生命科学研究所, 助教授 (90222166)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | regulatory T cells / Foxp3 / commitment |
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| Research Abstract |
1.Regulatory T cells develop in the thymus as other normal CD4+ T cells. However, it is not clear how regulatory T cells, which express their master gene Foxp3, differentiate and how regulatory T cells are selected in the thymus. We take an advantage to utilized moth cytochrome C (MCC) specific TCR transgenic mice in which three different peptides being recognized by the TCR with different affinities were expressed. In the TCR transgenic mice expressing an antigen peptide with a moderate affinity to the TCR (an altered peptide ligand of MCC88-103 with one amino acid mutation), the higher ratio of thymocytes differentiated into Foxp3+CD25+CD4+ thymocytes. In contrast, the TCR transgenic mice without endogenous TCRs by lacking RAG2 expression had almost no Foxp3+CD25+CD4+thymocytes. The expression of c-Krox was observed in the thymocytes differentiating toward CD4 but not so much in the thymocytes differentiating to regulatory T cells. Other transcription factors, GATA3 and Tox, known to be important for CD4+ thymocytes development, were expressed in both thymocytes differentiating to normal CD4+ and Foxp3+CD4+. We are now trying to isolating genes being expressed only in the thymocytes differentiating to Foxp3+CD4+ thymocyte by using a subtraction protocol based on PCR. 2.TGF-β1 is expressed upon antigen stimualation by regulatory T cells developed in this mouse model. As it is known that TGF-β1 is important to maintain the expression of Foxp3 in regulatory T cells, we investigated how the expression of TGF-β1 is regulated. We found that the TGF-β1 expression in regulatory T cells is regulated by NFAT activation.
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