| Project/Area Number |
15078204
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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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| Review Section |
Biological Sciences
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| Research Institution | Kyoto University |
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Principal Investigator |
MINATO Nagahiro Kyoto University, Graduate School of Biostuclies, Dept of Immunology and Cell Biology, Professor, 生命科学研究科, 教授 (40137716)
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| Co-Investigator(Kenkyū-buntansha) |
服部 雅一 京都大学, 生命科学研究科, 助教授 (40211479)
田中 義正 京都大学, 生命科学研究科, 助手 (90280700)
福井 宣規 九州大学, 生体防御医学研究所, 助教授 (60243961)
木梨 達雄 京都大学, 医学研究科, 教授 (30202039)
渡邊 武 九州大学, 生体防御医学研究所, 教授 (40028684)
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| Project Period (FY) |
2003 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥157,800,000 (Direct Cost: ¥157,800,000)
Fiscal Year 2006: ¥30,400,000 (Direct Cost: ¥30,400,000)
Fiscal Year 2005: ¥30,400,000 (Direct Cost: ¥30,400,000)
Fiscal Year 2004: ¥29,000,000 (Direct Cost: ¥29,000,000)
Fiscal Year 2003: ¥68,000,000 (Direct Cost: ¥68,000,000)
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| Keywords | Immune surveillance / Tumor immunity / Leukemia / Immune suppression / SPA-1 / Tumor immunotherapy / T cell responsiveness / Memory T cells / G蛋白 / T細胞 / Rap1 / 自己免疫病 / 自己抗体 / 造血幹細胞 / ループス腎炎 / レセプター編集 / 遺伝子ノックアウトマウス / 骨髄幹細胞異常症 / 免疫不全 / 抗DNA抗体 / アナジー / 低分子G蛋白 / 癌抑制遺伝子 / 免疫記憶 |
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| Research Abstract |
In this project, we aimed to study on the immunological surveillance mechanisms against tumor cells using naturally occurring tumor models in mice. The major achievements were as follows. (0 We found that SPA-1 KO mice naturally develop a spectrum of myeloproliferative disorders including chronic myeloid leukemia of long latency. The diseases highly resembled human myeloproliferative diseases, and SPA-1 KO mice were considered to provide an excellent model to study the roles of immune system during the naturally occurring malignancy (2) It was found that SPA-1 KO mice gradually developed CD4 T cell dysfunction preceding the leukemia development, and it was suggested that the T cell dysfunction during the preleukemic stage might contribute to the frank leukemia development (3) After overt development of systemic leukemia, the mice rapidly developed severe CD4 T cell unresponsiveness. This was ascribed to the progressive increase in PD-1+ CD4 T cells with memory phenotype, which were totally refractory to the TCR stimulation. Although exact mechanisms for the T cell unresponsiveness remained to be investigated, it was strongly suggested that marked increase in such a refractory T cell population contributed to the rapid progression of systemic leukemia leading to death. Future understanding of the mechanisms for leukemia cells to induce the T cell unresponsiveness and the development of the means to counteract the phenomenon should provide a hopeful approach to rescue the immune surveillance against tumor cells for controlling malignancy
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