Long-term maintenance of lung resident memory T cells is mediated by persistent antigen.

Mucosal Immunology
Ida E UddbäckJan P Christensen

Abstract

Tissue-resident memory T cells (TRM) in the lungs are pivotal for protection against repeated infection with respiratory viruses. However, the gradual loss of these cells over time and the associated decline in clinical protection represent a serious limit in the development of efficient T cell based vaccines against respiratory pathogens. Here, using an adenovirus expressing influenza nucleoprotein (AdNP), we show that CD8 TRM in the lungs can be maintained for at least 1 year post vaccination. Our results reveal that lung TRM continued to proliferate in situ 8 months after AdNP vaccination. Importantly, this required airway vaccination and antigen persistence in the lung, as non-respiratory routes of vaccination failed to support long-term lung TRM maintenance. In addition, parabiosis experiments show that in AdNP vaccinated mice, the lung TRM pool is also sustained by continual replenishment from circulating memory CD8 T cells that differentiate into lung TRM, a phenomenon not observed in influenza-infected parabiont partners. Concluding, these results demonstrate key requirements for long-lived cellular immunity to influenza virus, knowledge that could be utilized in future vaccine design.

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Citations

Jun 9, 2020·International Immunology·Shiki Takamura
Dec 18, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Veronica MartiniElma Tchilian
Mar 24, 2021·The Journal of Experimental Medicine·Karolina OkłaWeiping Zou
May 29, 2021·Frontiers in Immunology·Pankaj AhluwaliaRavindra Kolhe
May 18, 2021·Advanced Therapeutics·Frances C Knight, John T Wilson
Jun 6, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Veronica A DavéMartin Prlic
Jun 24, 2021·The Journal of Experimental Medicine·Kurt B Pruner, Marion Pepper
Jul 28, 2021·Nature Reviews. Immunology·Ed C Lavelle, Ross W Ward
Dec 18, 2021·Seminars in Respiratory and Critical Care Medicine·Tom D Y ReijndersTom van der Poll
Jan 28, 2022·EBioMedicine·Aqu AluXiawei Wei

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Methods Mentioned

BETA
bronchoalveolar
lavage
flow cytometry
FCS

Software Mentioned

TreeStar
FlowJo
Zen

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