| Project/Area Number |
11694241
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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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 | Institute of Basic Medical Sciences, University of Tsukuba |
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Principal Investigator |
NAKAUCHI Hiromistu Inst.of Basic Med.Sci., Univ of Tsukuba, Professor, 基礎医学系, 教授 (40175485)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHAMA Yosuke Inst.of Genome Research., Univ of Tokushima, Professor, ゲノム機能研究センター, 教授 (20183858)
SHIBUYA Kazuko Inst.of Clinical Med.Sci., Univ of Tsukuba, Lecturer, 臨床医学系, 講師 (00302406)
SHIBUYA Akira Inst.of Basic Med.Sci., Univ of Tsukuba, Associate Professor, 基礎医学系, 助教授 (80216027)
TAHARA Satoko JSTS,Research fellow, 特別研究員
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | NK cells / granuloma / inhibitory receptor / LFA-1 / DNAM-1 / adhesion molecule / Fc receptor / NKT cells / Fc受容体 / 肉芽腫 / Mycobacterium |
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| Research Abstract |
1) In collaboration with Dr.Gabriel Gahchelin of Pasteur Institute in Paris, France, we identified the role of NKT cells in granuroma formation induced by mycobacterium. NKT cells play a key role in the intial phase of granuloma formation. J α 281 gene knockout mice which lack NKT cells showed significantly reduced granuloma formation.
2) In collaboration with Dr.Lewis Lanier of University of San Francisco, we clarified the role of DNAM-1 in the signal transduction from LFA-1. Stimulation of T cell receptor gives LFA-1 an inside-out signal that in turn increases the ligand binding affinity and an association of LFA-1 with DNAM-1. Upon interaction with ligands, LFA-1 associates with a src family tyrosine kinase Fyn which phosphorylates DNAM-1 to transduce signals in side the cell.
3) A gene encoding a Fc receptor for lgM and lgA was isolated. We not only characterized its structure and expression, but also clarified its role in early phase of immunological defense system against microbes.
4) In order to stufdy the role of Notch signals in T cell development, Hes-1 gene was introduced into immature T cells using a retroviral vector. Transduced cells were cultured using fetal thymus organ culture system. Forced expression of Hes-1 increased cell growth but did not alter the proportion of CD4/CD8 T cell. Molecules other than Hes-1in the Notch signaling system seem to be responsible for CD4/CD8 commitment of T lymphoid cells.
5) A novel receptor specfically expressed in NK cells and macrophages has been isolated. This receptor with an Ig-like domain may serve as an inhibitory type receptor for NK cells.
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