Programs for the persistence, vigilance and control of human CD8 + lung-resident memory T cells

Pleun Hombrink; Christina Helbig; Ronald A. Backer; Berber Piet; Anna E. Oja; Regina Stark; Giso Brasser; Aldo Jongejan; René E. Jonkers; Benjamin Nota; Onur Basak; Hans C. Clevers; Perry D. Moerland; Derk Amsen; René A.W. Van Lier

doi:10.1038/ni.3589

Programs for the persistence, vigilance and control of human CD8 + lung-resident memory T cells

Pleun Hombrink, Christina Helbig, Ronald A. Backer, Berber Piet, Anna E. Oja, Regina Stark, Giso Brasser, Aldo Jongejan, René E. Jonkers, Benjamin Nota, Onur Basak, Hans C. Clevers, Perry D. Moerland, Derk Amsen, René A.W. Van Lier

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Abstract

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.

Original language	English
Pages (from-to)	1467-1478
Number of pages	12
Journal	Nature Immunology
Volume	17
Issue number	12
DOIs	https://doi.org/10.1038/ni.3589
Publication status	Published - 1 Dec 2016
Externally published	Yes

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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. (2016). Programs for the persistence, vigilance and control of human CD8 + lung-resident memory T cells. Nature Immunology, 17(12), 1467-1478. https://doi.org/10.1038/ni.3589

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title = "Programs for the persistence, vigilance and control of human CD8 + lung-resident memory T cells",

abstract = "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.",

author = "Pleun Hombrink and Christina Helbig and Backer, {Ronald A.} and Berber Piet and Oja, {Anna E.} and Regina Stark and Giso Brasser and Aldo Jongejan and Jonkers, {Ren{\'e} E.} and Benjamin Nota and Onur Basak and Clevers, {Hans C.} and Moerland, {Perry D.} and Derk Amsen and {Van Lier}, {Ren{\'e} A.W.}",

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AU - Hombrink, Pleun

AU - Helbig, Christina

AU - Backer, Ronald A.

AU - Piet, Berber

AU - Oja, Anna E.

AU - Stark, Regina

AU - Brasser, Giso

AU - Jongejan, Aldo

AU - Jonkers, René E.

AU - Nota, Benjamin

AU - Basak, Onur

AU - Clevers, Hans C.

AU - Moerland, Perry D.

AU - Amsen, Derk

AU - Van Lier, René A.W.

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AB - 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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Programs for the persistence, vigilance and control of human CD8 + lung-resident memory T cells

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