Investigation of the role of virus-specific stem cell-like memory T-cells in the patients with ATL and their therapeutic application
| Project/Area Number |
18K07292
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
TANAKA YUKIE 東京医科歯科大学, 統合研究機構, 助教 (10814197)
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| Co-Investigator(Kenkyū-buntansha) |
小林 誠一郎 東京大学, 医科学研究所, 助教 (70376622)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | HTLV-1 / 幹細胞様メモリーT細胞 / HLA-A24 / HTLV-1 Tax / ステムセルメモリーT細胞 / シングルセル解析 / 成人Ｔ細胞性白血病 / 免疫学 |
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| Outline of Final Research Achievements |
In this study, we analyzed stem cell memory T cells (TSCMs) of HTLV-1 Tax-CTLs. The results showed that TSCMs of Tax-CTLs, although rare, are present in the peripheral blood of HTLV-1 carriers and have very strong reactivity to Tax antigens in the in vitro experiments, and that various Tax-CTL memory clones source TSCMs, especially Tax-CTLs shared by HLA-A24 positive HTLV-1 infected individuals, are preferentially differentiated and proliferated from TSCM. It is strongly suggested that TSCMs of shared Tax-CTLs are promoted to differentiate and proliferate within HTLV-1 carriers, allowing for continuous surveillance of virus growth as dominant memory Tax-CTLs for a long period of time.
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| Academic Significance and Societal Importance of the Research Achievements |
Tax-CTLの幹細胞様T細胞がHTLV-1キャリア末梢血中に長期間存在すること、またそれらがTax抗原に対して極めて強い反応性を発揮し、メモリーTax-CTLの供給源であることを明らかにした。本研究の成果は、ATL発症抑制機構にTax-CTL幹細胞様T細胞が非常に重要であることを示したが、今後、自己血中のTax-CTL幹細胞様T細胞の増殖法を確立することで、日本人に最も多いHLA-A24陽性HTLV-1感染者を対象にした持続的CTL効果が期待できる幹細胞様T細胞の特性を活かした細胞療法の開発への貢献が予想される。
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Report
(5 results)
Research Products
(7 results)
