title: Programs for the persistence, vigilance and control of human CD8+lung-resident memory T cells.
abstract: Tissue-resident memory T cells (TRMcells) in the airways mediate protection against respiratory infection. We characterized TRMcells expressing integrin αE(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 TRMcells 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+TRMcells, including Notch. Genetic and pharmacological experiments with mice revealed that Notch activity was required for the maintenance of CD103+TRMcells. We have thus identified specialized programs underlying the residence, persistence, vigilance and tight control of human lung TRMcells.
authors: Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands.
authors: Pleun
authors: P
authors: Hombrink
authors: Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands.
authors: Christina
authors: C
authors: Helbig
authors: Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands.
authors: Ronald A
authors: RA
authors: Backer
authors: Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands.
authors: Berber
authors: B
authors: Piet
authors: Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands.
authors: Anna E
authors: AE
authors: Oja
authors: Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands.
authors: Regina
authors: R
authors: Stark
authors: Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands.
authors: Giso
authors: G
authors: Brasser
authors: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, the Netherlands.
authors: Aldo
authors: A
authors: Jongejan
authors: Department of Respiratory Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors: René E
authors: RE
authors: Jonkers
authors: Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands.
authors: Benjamin
authors: B
authors: Nota
authors: Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences), Utrecht, the Netherlands.
authors: Onur
authors: O
authors: Basak
authors: Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences), Utrecht, the Netherlands.
authors: Hans C
authors: HC
authors: Clevers
authors: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, the Netherlands.
authors: Perry D
authors: PD
authors: Moerland
authors: Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands.
authors: Derk
authors: D
authors: Amsen
authors: Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands.
authors: René A W
authors: http://orcid.org/0000-0002-3201-7144
authors: RA
authors: van Lier
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D039001:Integrin alpha Chains / Q000378:metabolism; D008168:Lung / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D051883:Receptor, Notch2 / Q000235:genetics / Q000378:metabolism*; D012141:Respiratory Tract Infections / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D039001:Integrin alpha Chains; C497762:Notch1 protein, mouse; C497765:Notch2 protein, mouse; D051881:Receptor, Notch1; D051883:Receptor, Notch2; C091367:alpha E integrins