title: RSV-specific airway resident memory CD8+ T cells and differential disease severity after experimental human infection.
abstract: In animal models, resident memory CD8+ T (Trm) cells assist in respiratory virus elimination but their importance in man has not been determined. Here, using experimental human respiratory syncytial virus (RSV) infection, we investigate systemic and local virus-specific CD8+ T-cell responses in adult volunteers. Having defined the immunodominance hierarchy, we analyse phenotype and function longitudinally in blood and by serial bronchoscopy. Despite rapid clinical recovery, we note surprisingly extensive lower airway inflammation with persistent viral antigen and cellular infiltrates. Pulmonary virus-specific CD8+ T cells display a CD69+CD103+ Trm phenotype and accumulate to strikingly high frequencies into convalescence without continued proliferation. While these have a more highly differentiated phenotype, they express fewer cytotoxicity markers than in blood. Nevertheless, their abundance before infection correlates with reduced symptoms and viral load, implying that CD8+ Trm cells in the human lung can confer protection against severe respiratory viral disease when humoral immunity is overcome.
authors.affiliation: National Heart and Lung Institute, Imperial College London, London W2 1PG, UK.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Jozwik
authors.affiliation: National Heart and Lung Institute, Imperial College London, London W2 1PG, UK.
authors.forename: Maximillian S
authors.initials: MS
authors.lastname: Habibi
authors.affiliation: National Heart and Lung Institute, Imperial College London, London W2 1PG, UK.
authors.forename: Allan
authors.initials: A
authors.lastname: Paras
authors.affiliation: National Heart and Lung Institute, Imperial College London, London W2 1PG, UK.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: National Heart and Lung Institute, Imperial College London, London W2 1PG, UK.
authors.forename: Aleks
authors.initials: A
authors.lastname: Guvenel
authors.affiliation: National Heart and Lung Institute, Imperial College London, London W2 1PG, UK.
authors.forename: Jaideep
authors.initials: J
authors.lastname: Dhariwal
authors.affiliation: National Heart and Lung Institute, Imperial College London, London W2 1PG, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Almond
authors.affiliation: National Heart and Lung Institute, Imperial College London, London W2 1PG, UK.
authors.forename: Ernie H C
authors.initials: EHC
authors.lastname: Wong
authors.affiliation: National Heart and Lung Institute, Imperial College London, London W2 1PG, UK.
authors.forename: Annemarie
authors.initials: A
authors.lastname: Sykes
authors.affiliation: Centre for Infectious Disease, Division of Vaccine Discovery, La Jolla Institute of Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Maybeno
authors.affiliation: National Heart and Lung Institute, Imperial College London, London W2 1PG, UK.
authors.forename: Jerico
authors.initials: J
authors.lastname: Del Rosario
authors.affiliation: National Heart and Lung Institute, Imperial College London, London W2 1PG, UK.
authors.forename: Maria-Belen
authors.initials: MB
authors.lastname: Trujillo-Torralbo
authors.affiliation: National Heart and Lung Institute, Imperial College London, London W2 1PG, UK.
authors.forename: Patrick
authors.initials: P
authors.lastname: Mallia
authors.affiliation: Centre for Infectious Disease, Division of Vaccine Discovery, La Jolla Institute of Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA.
authors.forename: John
authors.initials: J
authors.lastname: Sidney
authors.affiliation: Centre for Infectious Disease, Division of Vaccine Discovery, La Jolla Institute of Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA.
authors.forename: Bjoern
authors.identifier: http://orcid.org/0000-0002-8457-6693
authors.initials: B
authors.lastname: Peters
authors.affiliation: National Heart and Lung Institute, Imperial College London, London W2 1PG, UK.
authors.forename: Onn Min
authors.initials: OM
authors.lastname: Kon
authors.affiliation: Centre for Infectious Disease, Division of Vaccine Discovery, La Jolla Institute of Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.affiliation: National Heart and Lung Institute, Imperial College London, London W2 1PG, UK.
authors.forename: Sebastian L
authors.initials: SL
authors.lastname: Johnston
authors.affiliation: National Heart and Lung Institute, Imperial College London, London W2 1PG, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Openshaw
authors.affiliation: National Heart and Lung Institute, Imperial College London, London W2 1PG, UK.
authors.forename: Christopher
authors.identifier: http://orcid.org/0000-0003-0914-920X
authors.initials: C
authors.lastname: Chiu
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000821:virology; D008297:Male; D051379:Mice; D008875:Middle Aged; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology / Q000502:physiology; D055815:Young Adult