Populations of CD8+ lung-resident memory T (TRM) cells persist in the interstitium and epithelium (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 about whether tissue-circulating effector memory T (TEM) cells are the source of these newly recruited cells. Here we definitively demonstrate that CD8+ TRM cells in the lung airways are not derived from TEM cells in the circulation, but are seeded continuously by TRM cells from the lung interstitium. This process is driven by CXCR6 that is expressed uniquely on TRM cells but not TEM cells. We further demonstrate that the lung interstitium CD8+ TRM cell population is also maintained independently of TEM cells 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 cells and clarify the mechanisms underlying their maintenance.
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September 26 2019
Interstitial-resident memory CD8+ T cells sustain frontline epithelial memory in the lung
Shiki Takamura
,
1
Department of Immunology, Kindai University Faculty of Medicine, Osaka, Japan
Correspondence to Shiki Takamura: takamura@med.kindai.ac.jp
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Shigeki Kato
,
Shigeki Kato
1
Department of Immunology, Kindai University Faculty of Medicine, Osaka, Japan
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Chihiro Motozono
,
Chihiro Motozono
2
Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
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Takeshi Shimaoka
,
Takeshi Shimaoka
3
Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan
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Satoshi Ueha
,
Satoshi Ueha
3
Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan
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Kazuhiko Matsuo
,
Kazuhiko Matsuo
4
Division of Chemotherapy, Kindai University Faculty of Pharmacy. Osaka, Japan
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Kosuke Miyauchi
,
Kosuke Miyauchi
5
Laboratory for Cytokine Regulation, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Kanagawa, Japan
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Tomoko Masumoto
,
Tomoko Masumoto
1
Department of Immunology, Kindai University Faculty of Medicine, Osaka, Japan
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Asami Katsushima
,
Asami Katsushima
1
Department of Immunology, Kindai University Faculty of Medicine, Osaka, Japan
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Takashi Nakayama
,
Takashi Nakayama
4
Division of Chemotherapy, Kindai University Faculty of Pharmacy. Osaka, Japan
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Michio Tomura
,
Michio Tomura
6
Laboratory of Immunology, Faculty of Pharmacy, Osaka Otani University, Osaka, Japan
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Kouji Matsushima
,
Kouji Matsushima
3
Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan
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Masato Kubo
,
Masato Kubo
5
Laboratory for Cytokine Regulation, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Kanagawa, Japan
7
Division of Molecular Pathology, Research Institute for Biomedical Science, Tokyo University of Science, Chiba, Japan
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Masaaki Miyazawa
Masaaki Miyazawa
1
Department of Immunology, Kindai University Faculty of Medicine, Osaka, Japan
8
Anti-Aging Center, Kindai University, Osaka, Japan
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Shiki Takamura
1
Department of Immunology, Kindai University Faculty of Medicine, Osaka, Japan
Shigeki Kato
1
Department of Immunology, Kindai University Faculty of Medicine, Osaka, Japan
Chihiro Motozono
2
Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
Takeshi Shimaoka
3
Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan
Satoshi Ueha
3
Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan
Kazuhiko Matsuo
4
Division of Chemotherapy, Kindai University Faculty of Pharmacy. Osaka, Japan
Kosuke Miyauchi
5
Laboratory for Cytokine Regulation, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Kanagawa, Japan
Tomoko Masumoto
1
Department of Immunology, Kindai University Faculty of Medicine, Osaka, Japan
Asami Katsushima
1
Department of Immunology, Kindai University Faculty of Medicine, Osaka, Japan
Takashi Nakayama
4
Division of Chemotherapy, Kindai University Faculty of Pharmacy. Osaka, Japan
Michio Tomura
6
Laboratory of Immunology, Faculty of Pharmacy, Osaka Otani University, Osaka, Japan
Kouji Matsushima
3
Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan
Masato Kubo
5
Laboratory for Cytokine Regulation, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Kanagawa, Japan
7
Division of Molecular Pathology, Research Institute for Biomedical Science, Tokyo University of Science, Chiba, Japan
Masaaki Miyazawa
1
Department of Immunology, Kindai University Faculty of Medicine, Osaka, Japan
8
Anti-Aging Center, Kindai University, Osaka, Japan
Correspondence to Shiki Takamura: takamura@med.kindai.ac.jp
J Exp Med (2019) 216 (12): 2736-2747.
Article history
Received:
March 27 2019
Revision Received:
July 10 2019
Accepted:
September 04 2019
Citation
Shiki Takamura, Shigeki Kato, Chihiro Motozono, Takeshi Shimaoka, Satoshi Ueha, Kazuhiko Matsuo, Kosuke Miyauchi, Tomoko Masumoto, Asami Katsushima, Takashi Nakayama, Michio Tomura, Kouji Matsushima, Masato Kubo, Masaaki Miyazawa; Interstitial-resident memory CD8+ T cells sustain frontline epithelial memory in the lung. J Exp Med 2 December 2019; 216 (12): 2736–2747. doi: https://doi.org/10.1084/jem.20190557
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