| Project/Area Number |
10670300
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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 | KYOTO UNIVERSITY |
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Principal Investigator |
HATTORI Masakazu Kyoto University, Graduate school of Biostudies, Dept. of Immunology and Cell Biology, Associate Professor, 生命科学研究科, 助教授 (40211479)
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| Co-Investigator(Kenkyū-buntansha) |
MINATO Nagahiro Kyoto University, Graduate school of Biostudies, Dept. of Immunology and Cell Biology, Professor, 生命科学研究科, 教授 (40137716)
KAGEYAMA Ryuichiro Kyoto University, Institute for Virus Research, Professor, ウイルス研究所, 教授 (80224369)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | Hesl / bHLH / T cell / RAG2 / Notchl / thymus / HES1 / T細胞増殖制御 / ストローマ細胞 / Pre T細胞 / T細胞初期分化 / double negative / TCR非依存性増殖 |
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| Research Abstract |
T cells undergo multiple of proliferation and differentiation in the thymus before final maturation, in which a number of transcriptional regulators are shown to control the distinct steps by regulating specific sets of gene activation. Hes 1, a mammalian counterpart of Drosophila Hairy and Enhancer of split, is a member of basic helix-loop-helix (bHLH) transcriptional regulators and expressed in the developing nervous tissues and thymus in normal embryo. Fetus of Hes 1 deficient mice were found to exhibit severe thymus dysplasia in addition of the anomalous development of nervous system. Transfer experiments of fetal liver into RAG2 deficient mice indicate that Hes 1 (-1-) fetal liver cells mostly totally failed to repopulate the thymus while B cells and other hematopoietic cells were reconstituted normally. Detailed analysis revealed that the differentiation of T cells in thymus from Hes 1 (-1-) stem cells was arrested at the earliest recognizable stage, CD4ィイD1-ィエD1CD8ィイD1-ィエD1CD44ィイD1+ィエD1CD25ィイD1-ィエD1 with no evidence of TCR gene rearrangement. The results clearly indicate that Hes 1 is indispensably required cell-autonomously for the earliest expansion of pro-T cells in the thymus. Hes 1 is shown to be at the down-stream of Notch signal pathway, and it was reported by other group that conditional Notch 1 gene targeting in adult mice show similar specific effects on thymocyte development. Using appropriate cell systems, we are currently studying the molecular mechanisms, in which Hesl controls the proliferation and differentiation at the specificstages of T cell development.
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