Mechanisms by which lung-resident memory CD8 T cells are maintained
| Project/Area Number |
16K08850
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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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| Research Field |
Immunology
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| Research Institution | Kindai University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
本園 千尋 九州大学, 医学研究院, 助教 (10642910)
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| Research Collaborator |
TOMURA Michio
FUKUYAMA Satoshi
MIYAZAWA Masaaki
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | メモリーCD8T細胞 / 組織滞在型 / 肺 / 感染防御 / インフルエンザウイルス / 滞在型メモリー / 免疫記憶 / CD8T細胞 / 肺粘膜 / 粘膜免疫 |
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| Outline of Final Research Achievements |
Populations of CD8 lung-resident memory T (TRM) cells persist in the interstitium and airways following recovery from respiratory virus infections. While it is clear that CD8 TRM cells in the airways are dynamically maintained via the continuous recruitment of new cells, there is a vigorous debate whether tissue-circulating effector memory T (TEM) cells are the source of these newly recruited cells. Here we definitively demonstrate that CD8 TRM in the lung airways are not derived from TEM in the circulation, but are seeded continuously by TRM from the lung interstitium. This process is driven by CXCR6 that is expressed on TRM, but not TEM. We further demonstrate that the lung interstitium CD8 TRM population is also maintained independently of TEM via a homeostatic proliferation mechanism. Taken together, these data show that lung memory CD8 TRM cells in the lung interstitium and airways are compartmentally separated from TEM and clarify the mechanisms underlying their maintenance.
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| Academic Significance and Societal Importance of the Research Achievements |
現行のインフルエンザワクチン（ウイルス表面タンパク質の皮内投与）により誘導される免疫応答は特定の株に対する全身性抗体反応であり、侵入部位である肺局所での感染防御効果は期待できず、頻繁に発生するウイルス表面抗原変異にも対応が困難である。一方、CD8T細胞はウイルス株間で高度に保存された内部タンパク質を標的とすることで交差反応性を示す事は周知である。従って、病原体侵入部位に長期間維持される滞在型メモリーCD8T細胞を効果的に誘導・維持することが将来のワクチン開発に求められる。本研究ではその維持機構の一端を解明した。今後は肺滞在型メモリーCD8T細胞誘導機構の解明が待たれる。
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] B7-H3 negatively modulates CTL-mediated cancer immunity2018
Author(s)
Yonesaka K, Haratani K, Takamura S, Sakai H, Kato R, Takegawa N, Takahama T, Tanaka K, Hayashi H, Takeda M, Kato S, Maenishi O, Sakai K, Chiba Y, Okabe T, Kudo K, Hasegawa Y, Kaneda H, Yamato M, Hirotani K, Miyazawa M, Nishio K, Nakagawa K.
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Journal Title
Clin Cancer Res.
Volume: -
Issue: 11
Pages: 2653-2664
DOI
Related Report
Peer Reviewed
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[Journal Article] Specific niches for lung-resident memory CD8+ T cells at the site of tissue regeneration enable CD69-independent maintenance.2016
Author(s)
Takamura, S., H. Yagi, Y. Hakata, C. Motozono, S. R. McMaster, T. Masumoto, M. Fujisawa, T. Chikaishi, J. Komeda, J. Itoh, M. Umemura, A. Kyusai, M. Tomura, T. Nakayama, D. L. Woodland, J. E. Kohlmeier, and M. Miyazawa
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Journal Title
The Journal of Experimental Medicine
Volume: 213
Issue: 13
Pages: 3057-3073
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] Antigen presentation by pulmonary macrophages drives the establishment of lung-resident CD8 T cell memory2018
Author(s)
Takamura S, Dunbar PR, Cartwright EK, Wein AN, Tsukamoto T, Li ZR, Kuma Nr, Uddback I, Hawyard SL, Ueha S, and Kohlmeier JE
Organizer
日本免疫学会学術集会
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