RSV-specific airway resident memory CD8+ T cells and differential disease severity after experimental human infection

Agnieszka Jozwik, Maximillian S. Habibi, Allan Paras, Jie Zhu, Aleks Guvenel, Jaideep Dhariwal, Mark Almond, Ernie H. C. Wong, Annemarie Sykes, Matthew Maybeno, Jerico Del Rosario, Maria-Belen Trujillo-Torralbo, Patrick Mallia, John Sidney, Bjoern Peters, Onn Min Kon, Alessandro Sette, Sebastian L. Johnston, Peter J. Openshaw and Christopher Chiu ()
Additional contact information
Agnieszka Jozwik: National Heart and Lung Institute, Imperial College London
Maximillian S. Habibi: National Heart and Lung Institute, Imperial College London
Allan Paras: National Heart and Lung Institute, Imperial College London
Jie Zhu: National Heart and Lung Institute, Imperial College London
Aleks Guvenel: National Heart and Lung Institute, Imperial College London
Jaideep Dhariwal: National Heart and Lung Institute, Imperial College London
Mark Almond: National Heart and Lung Institute, Imperial College London
Ernie H. C. Wong: National Heart and Lung Institute, Imperial College London
Annemarie Sykes: National Heart and Lung Institute, Imperial College London
Matthew Maybeno: Centre for Infectious Disease, La Jolla Institute of Allergy and Immunology
Jerico Del Rosario: National Heart and Lung Institute, Imperial College London
Maria-Belen Trujillo-Torralbo: National Heart and Lung Institute, Imperial College London
Patrick Mallia: National Heart and Lung Institute, Imperial College London
John Sidney: Centre for Infectious Disease, La Jolla Institute of Allergy and Immunology
Bjoern Peters: Centre for Infectious Disease, La Jolla Institute of Allergy and Immunology
Onn Min Kon: National Heart and Lung Institute, Imperial College London
Alessandro Sette: Centre for Infectious Disease, La Jolla Institute of Allergy and Immunology
Sebastian L. Johnston: National Heart and Lung Institute, Imperial College London
Peter J. Openshaw: National Heart and Lung Institute, Imperial College London
Christopher Chiu: National Heart and Lung Institute, Imperial College London

Nature Communications, 2015, vol. 6, issue 1, 1-17

Abstract: 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.

Date: 2015
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms10224 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms10224

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms10224

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().