Programs for the persistence, vigilance and control of human CD8+ lung-resident memory T cells
Open accessAbstract
Tissue-resident memory T cells (T RM cells) in the airways mediate protection against respiratory infection. We characterized T RM cells expressing integrin α E (CD103) that reside within the epithelial barrier of human lungs. These cells had specialized profiles of chemokine receptors and adhesion molecules, consistent with their unique localization. Lung T RM cells were poised for rapid responsiveness by constitutive expression of deployment-ready mRNA encoding effector molecules, but they also expressed many inhibitory regulators, suggestive of programmed restraint. A distinct set of transcription factors was active in CD103+ T RM cells, including Notch. Genetic and pharmacological experiments with mice revealed that Notch activity was required for the maintenance of CD103+ T RM cells. We have thus identified specialized programs underlying the residence, persistence, vigilance and tight control of human lung T RM cells.
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Inhibitory receptors PD-1, CTLA-4, and 2B4 are expressed by Trm.
“Inhibitory receptors PD-1, CTLA-4, and 2B4 are expressed by Trm [241, 256, 257], which may control the effector function of these Trm.”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [256]
The preferred collagenase used by multiple research groups is collagenase IV.
“The preferred collagenase used by multiple research groups is collagenase IV [253, 256, 257, 267].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [256]
Both CD8+ and CD4+ Trm have been identified in human skin, lung, intestines, salivary glands, bone marrow, brain, spleen, tonsils, and lymph nodes.
“Both CD8+ and CD4+ Trm have been identified in the human skin, lung, intestines, salivary glands, bone marrow, brain, spleen, tonsils, and lymph nodes [241, 244, 246, 253-259].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [256]
Trm that co-express CD69 and CD103 are mainly found in the skin, lung, salivary glands, brain, and intestines.
“Trm that co-express CD69 and CD103 are mainly found in the skin, lung, salivary glands, brain, and intestines [241, 256-258].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [256]
TRM represent a first anti-viral defence, ready to release a high load of IFN-γ and TNF upon TCR stimulation.
“In fact, they represent a first anti-viral defence, ready to release a high load of IFN-γ and TNF upon TCR stimulation(129).”
From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [129]
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- Authors
- Hombrink, P., Helbig, C., Backer, R. A., Piet, B., Oja, A. E., Stark, R., Brasser, G., Jongejan, A., Jonkers, R. E., Nota, B., Basak, O., Clevers, H. C., Moerland, P. D., Amsen, D., & van Lier, R. A. W.
- Affiliations
- Sanquin (NL)
- Amsterdam UMC Location University of Amsterdam (NL)
- Royal Netherlands Academy of Arts and Sciences (NL)
- Corresponding author
- Amsen, Derk
- ORCID
- Venue
- Nature Immunology
- Published
- 2016-10-24
- Volume
- 17
- Issue
- 12
- Pages
- 1467-1478
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2533830780
- Cited by
- 455
- References
- 57
- Citations by year
- 2026: 23 · 2025: 41 · 2024: 36 · 2023: 42 · 2022: 48 · 2021: 73 · 2020: 66 · 2019: 52 · 2018: 47 · 2017: 24 · 2016: 2 · 2013: 1
- FWCI
- 25.22
- Type
- journal article
- Language
- en
- Update notices
- erratum (2017-02-01)
- Open access
- green
- dspace.library.uu.nl
- Licence
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (submittedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion)
- Funders
- Alexander von Humboldt-Stiftung
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- tissue-resident memory T cells, lung-resident memory T cells, CD8+ T cells, CD103, Notch signaling, transcriptional programs, cellular metabolism, chemokine receptors, adhesion molecules, transcription factors, respiratory infections, airway epithelium, T cell persistence
- MeSH terms
- Animals, Cells, Cultured, Female, Humans, Immunologic Memory, Lung, Male, Mice, Inbred C57BL, Mice, Transgenic, Middle Aged, Orthomyxoviridae Infections, Respiratory Tract Infections, Antigens, CD, CD8-Positive T-Lymphocytes, Integrin alpha Chains, Mice, Receptor, Notch1, Receptor, Notch2, Influenza A Virus, H3N2 Subtype
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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