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

Angela Pizzolla, Thi H.O. Nguyen, Sneha Sant, Jade Jaffar, Tom Loudovaris, Stuart I. Mannering, Paul G. Thomas, Glen P. Westall, Katherine Kedzierska, Linda M. Wakim

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)721-733
Number of pages13
JournalJournal of Clinical Investigation
Volume128
Issue number2
DOIs
Publication statusPublished - 1 Feb 2018

Cite this

Pizzolla, A., Nguyen, T. H. O., Sant, S., Jaffar, J., Loudovaris, T., Mannering, S. I., ... Wakim, L. M. (2018). Influenza-specific lung-resident memory t cells are proliferative and polyfunctional and maintain diverse TCR profiles. Journal of Clinical Investigation, 128(2), 721-733. https://doi.org/10.1172/JCI96957
Pizzolla, Angela ; Nguyen, Thi H.O. ; Sant, Sneha ; Jaffar, Jade ; Loudovaris, Tom ; Mannering, Stuart I. ; Thomas, Paul G. ; Westall, Glen P. ; Kedzierska, Katherine ; Wakim, Linda M. / Influenza-specific lung-resident memory t cells are proliferative and polyfunctional and maintain diverse TCR profiles. In: Journal of Clinical Investigation. 2018 ; Vol. 128, No. 2. pp. 721-733.
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abstract = "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.",
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Pizzolla, A, Nguyen, THO, Sant, S, Jaffar, J, Loudovaris, T, Mannering, SI, Thomas, PG, Westall, GP, Kedzierska, K & Wakim, LM 2018, 'Influenza-specific lung-resident memory t cells are proliferative and polyfunctional and maintain diverse TCR profiles' Journal of Clinical Investigation, vol. 128, no. 2, pp. 721-733. https://doi.org/10.1172/JCI96957

Influenza-specific lung-resident memory t cells are proliferative and polyfunctional and maintain diverse TCR profiles. / Pizzolla, Angela; Nguyen, Thi H.O.; Sant, Sneha; Jaffar, Jade; Loudovaris, Tom; Mannering, Stuart I.; Thomas, Paul G.; Westall, Glen P.; Kedzierska, Katherine; Wakim, Linda M.

In: Journal of Clinical Investigation, Vol. 128, No. 2, 01.02.2018, p. 721-733.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Pizzolla, Angela

AU - Nguyen, Thi H.O.

AU - Sant, Sneha

AU - Jaffar, Jade

AU - Loudovaris, Tom

AU - Mannering, Stuart I.

AU - Thomas, Paul G.

AU - Westall, Glen P.

AU - Kedzierska, Katherine

AU - Wakim, Linda M.

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N2 - 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.

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