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J Exp Med. 2019 Sep 26. pii: jem.20190557. doi: 10.1084/jem.20190557. [Epub ahead of print]

Interstitial-resident memory CD8+ T cells sustain frontline epithelial memory in the lung.

Author information

1
Department of Immunology, Kindai University Faculty of Medicine, Osaka, Japan takamura@med.kindai.ac.jp.
2
Department of Immunology, Kindai University Faculty of Medicine, Osaka, Japan.
3
Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
4
Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan.
5
Division of Chemotherapy, Kindai University Faculty of Pharmacy. Osaka, Japan.
6
Laboratory for Cytokine Regulation, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Kanagawa, Japan.
7
Laboratory of Immunology, Faculty of Pharmacy, Osaka Otani University, Osaka, Japan.
8
Division of Molecular Pathology, Research Institute for Biomedical Science, Tokyo University of Science, Chiba, Japan.
9
Anti-Aging Center, Kindai University, Osaka, Japan.

Abstract

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.

PMID:
31558614
DOI:
10.1084/jem.20190557

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