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

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

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  • NSTL
  • Springer Nature
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.

RESPIRATORY SYNCYTIAL VIRUSCD8(+) T-CELLSCLEAR VIRUSINFLUENZAPROTECTIONIMMUNITYMICEEPITOPESVACCINEADULTS

Habibi, Maximillian S.、Jozwik, Agnieszka、Paras, Allan、Guvenel, Aleks、Dhariwal, Jaideep、Almond, Mark、Wong, Ernie H. C.、Sykes, Annemarie、Maybeno, Matthew、Del Rosario, Jerico、Trujillo-Torralbo, Maria-Belen、Mallia, Patrick、Sidney, John、Peters, Bjoern、Kon, Onn Min、Sette, Alessandro、Johnston, Sebastian L.、Openshaw, Peter J.、Zhu, Jie、Chiu, Christopher

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Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London W2 1PG, England

La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, Ctr Infect Dis, La Jolla, CA 92037 USA

2015

10.1038/ncomms10224

Nature Communications

Nature Communications

AHCI
ISSN：2041-1723
年,卷(期)：2015.6(Dec.)
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