RSV-specific airway resident memory CD8+ T cells and differential disease severity after experimental human infection
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Published version
Author(s)
Type
Journal Article
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 analyze 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. These are more highly differentiated but express fewer cytotoxicity markers than in blood, but their abundance prior to infection correlates with protection from more severe disease.
Date Issued
2015-12-21
Date Acceptance
2015-11-16
Citation
Nature Communications, 2015, 6, pp.1-17
ISSN
2041-1723
Publisher
Nature Publishing Group
Start Page
1
End Page
17
Journal / Book Title
Nature Communications
Volume
6
Copyright Statement
This work is licensed under a Creative Commons Attribution 4.0
International License. The images or other third party material in this
article are included in the article’s Creative Commons license, unless indicated otherwise
in the credit line; if the material is not included under the Creative Commons license,
users will need to obtain permission from the license holder to reproduce the material.
To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
International License. The images or other third party material in this
article are included in the article’s Creative Commons license, unless indicated otherwise
in the credit line; if the material is not included under the Creative Commons license,
users will need to obtain permission from the license holder to reproduce the material.
To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
License URL
Sponsor
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
National Institute for Health Research
Medical Research Council (MRC)
Wellcome Trust
Asthma UK
Asthma UK
Identifier
https://www.nature.com/articles/ncomms10224
Grant Number
G0902266
G1000758
G1000758
NF-SI-0513-10150
G0700552
087805/Z/08/Z
CH11SJ
CH11SJ
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
RESPIRATORY SYNCYTIAL VIRUS
T-CELLS
CLEAR VIRUS
PROTECTION
INFLUENZA
IMMUNITY
VACCINE
RESPONSES
EPITOPES
CHILDREN
Adolescent
Adult
Animals
CD8-Positive T-Lymphocytes
Cell Differentiation
Female
Humans
Immunologic Memory
Lung
Male
Mice
Middle Aged
Respiratory Syncytial Virus Infections
Respiratory Syncytial Viruses
Young Adult
Lung
CD8-Positive T-Lymphocytes
Animals
Humans
Mice
Respiratory Syncytial Viruses
Respiratory Syncytial Virus Infections
Cell Differentiation
Immunologic Memory
Adolescent
Adult
Middle Aged
Female
Male
Young Adult
Publication Status
Published
Article Number
10224
Date Publish Online
2015-12-21