| Project/Area Number |
05272102
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Research Institution | Osaka University |
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Principal Investigator |
HIRANO Toshio School of Medicine, Osaka University, Professor, 医学部, 教授 (40136718)
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| Co-Investigator(Kenkyū-buntansha) |
SUGAMURA Kazuo School of Medicine, Tohoku University, Professor, 医学部, 教授 (20117360)
SAKAGUCHI Nobuo School of Medicine, Kumamoto University, Professor, 医学部, 教授 (70192086)
SAITO Takashi School of Medicine, Chiba University, Professor, 医学部, 教授 (50205655)
NISHIKAWA Shin-ichi Faculty of Medicine, Kyoto University, Professor, 医学部, 教授 (60127115)
KATSURA Yoshimoto Chest Disease Research Institute, Kyoto University, Professor, 胸部疾患研究所, 教授 (90027095)
上出 利光 北海道大学, 免疫科学研究所, 教授 (00160185)
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥226,800,000 (Direct Cost: ¥226,800,000)
Fiscal Year 1995: ¥76,800,000 (Direct Cost: ¥76,800,000)
Fiscal Year 1994: ¥78,000,000 (Direct Cost: ¥78,000,000)
Fiscal Year 1993: ¥72,000,000 (Direct Cost: ¥72,000,000)
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| Keywords | lymphocyte lineage / signal transduction / tolerance / antigen receptor / cytokine / apoptosis / costimulatory factor / 骨髄ストローマ / サイトカイン受容体 / 補助因子受容体 / リンパ球初期分化 / クローナル除去 |
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| Research Abstract |
Using a serum independent pro-B cell cultivation method, the Nishikawa group discovered the important role of fyn kinase in the formation of the (fusion line). In addition, this group showed the use of Flk2 expression as a marker for definition of the most undifferentiated stage of pro-B cells. Along with demonstrating that differentiated thymic cells (c-kit+, CD44+, CD25-) can be divided into FcR+ and FcR- groups, the Katsura group showed that T cell lineage cells are definitively FcR+. The Sugamura group developed IL-2 receptor gamma chain mutant mice. The gamma chain mutant mice showed severe immunodeficiency due to a reduction in B and T lineage cells and a complete lack of NK cells. The Hirano group, demonstrated the participation of the JAK-STAT transduction pathway in IL-6 receptor-mediated signal transduction. In addition, this group demonstrated the critical role of STAT3 in IL-6 mediated macrophage cell division. The Saito group, using a mouse line developed by crossing a CD3 deficient mouse and a TCR-Tg mouse, demonstrated the relationship between TCR signal strength and T cell selection. Also, they demonstrated the importance of Jak3 in T cell proliferation. In addition to demonstrating the importance of p52 in /VpreB/ signal transduction in B cells, the Sakaguchi group also solved the structure of this newly discovered molecule. The Suda group reported the strong expression of FAS in fetal spleen cells as well as the expression of functional FAS on B cells due to LPS stimulation, thus demonstrating the role of Fas in the death of activated B cells. Also, this group demonstrated that, due to protein degradation of membrane-bound human Fas ligand, Fas can be secreted while maintaining its cytotolytic activity. Furthermore, the group developed a monoclonal specific for Fas ligand and established an ELISA assay for Fas ligand expression.
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