Influenza-specific lung-resident memory T cells are proliferative and polyfunctional and maintain diverse TCR profiles

The human lung harbors a large population of resident memory T cells (Trm cells). These cells are perfectly positioned to mediate rapid protection against respiratory pathogens such as influenza virus, a highly contagious respiratory pathogen that continues to be a major public health burden. Animal...

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Bibliographic Details
Published in:The Journal of clinical investigation 2018-02, Vol.128 (2), p.721-733
Main Authors: Pizzolla, Angela, Nguyen, Thi Ho, Sant, Sneha, Jaffar, Jade, Loudovaris, Tom, Mannering, Stuart I, Thomas, Paul G, Westall, Glen P, Kedzierska, Katherine, Wakim, Linda M
Format: Article
Language:English
Subjects:
Animal models
Biomedical research
CD8 antigen
Genetic crosses
Health aspects
Immunological memory
Influenza
Influenza research
Lungs
Lymphocytes T
Memory cells
Pandemics
Pathogens
Public health
Respiratory diseases
T cell antigen receptors
T cell receptors
Vaccines
Viruses
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Summary:The human lung harbors a large population of resident memory T cells (Trm cells). These cells are perfectly positioned to mediate rapid protection against respiratory pathogens such as influenza virus, a highly contagious respiratory pathogen that continues to be a major public health burden. Animal models show that influenza-specific lung CD8+ Trm cells are indispensable for crossprotection against pulmonary infection with different influenza virus strains. However, it is not known whether influenza-specific CD8+ Trm cells present within the human lung have the same critical role in modulating the course of the disease. Here, we showed that human lung contains a population of CD8+ Trm cells that are highly proliferative and have polyfunctional progeny. We observed that different influenza virus-specific CD8+ T cell specificities differentiated into Trm cells with varying efficiencies and that the size of the influenza-specific CD8+ T cell population persisting in the lung directly correlated with the efficiency of differentiation into Trm cells. To our knowledge, we provide the first ex vivo dissection of paired T cell receptor (TCR) repertoires of human influenza-specific CD8+ Trm cells. Our data reveal diverse TCR profiles within the human lung Trm cells and a high degree of clonal sharing with other CD8+ T cell populations, a feature important for effective T cell function and protection against the generation of viral-escape mutants.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI96957