Investigation of the role of virus-specific stem cell-like memory T-cells in the patients with ATL and their therapeutic application

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K07292
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: TANAKA YUKIE 東京医科歯科大学, 統合研究機構, 助教 (10814197)
• Co-Investigator(Kenkyū-buntansha): 小林 誠一郎 東京大学, 医科学研究所, 助教 (70376622)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: HTLV-1 / 幹細胞様メモリーT細胞 / HLA-A24

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.

Free Research Field

感染症免疫学

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。