| Project/Area Number |
18K07051
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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 49030:Experimental pathology-related
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| Research Institution | The University of Tokyo (2020-2021)
Institute of Physical and Chemical Research (2018-2019) |
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Principal Investigator |
Setoguchi Ruka 東京大学, 大学院薬学系研究科(薬学部), 准教授 (50415204)
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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: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 免疫 / 感染 / ウイルス / 免疫記憶 / サイトカイン / 記憶T細胞 |
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| Outline of Final Research Achievements |
How memory CD8 T cell numbers are stably maintained remain elusive. The requirement of CD4 help for memory CD8 T-cell homeostasis has been controversial, because their defective persistence is consistently seen in MHC class II (MHCII)-deficient, but not in other CD4 T cell-deficient, host mice. We hypothesized that a previously unidentified factor in MHCII-deficient mice may account for the defective memory CD8 T cell maintenance. We found that IFN response genes were up-regulated in memory CD8 T cells, and IFN-gamma, but not IFN-beta, levels were elevated, in MHCII-deficient mice. IFN-gamma neutralization restored memory CD8 T cell numbers in MHCII-deficient mice, whereas continuous IFN-gamma administrations reduced their numbers in WT mice. Furthermore, IFN-gamma upregulation, not in CD4-deficient but in MHCII-deficient mice, was observed mainly in colon and induced by the microbiota.
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| Academic Significance and Societal Importance of the Research Achievements |
現在メモリーT細胞の研究は、非リンパ系組織常在型メモリーT細胞およびメモリーT細胞の分化に必要な転写因子ネットワークの研究が盛んである。メモリーT細胞の量的維持機構は、免疫学的および臨床医学的重要性にも関わらず、IL-7、IL-15およびCD4 T細胞によるヘルプ以外にメカニズムは存在しないかの如く、新たな分子機構の報告はない。このような状況下で、本研究結果は炎症性サイトカインがメモリーCD8 T細胞の恒常性を破綻させるという新規制御機構を提唱できるものである。さらに、CD8 T細胞を標的としたワクチンの有効性向上につながる研究に発展する可能性があり社会的意義も大きい。
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