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

Tissue-resident memory T cells (T-RM) 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 T(RM)in the lungs can be maintained for at least 1 year post vaccination. Our results reveal that lung T(RM)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 T(RM)maintenance. In addition, parabiosis experiments show that in AdNP vaccinated mice, the lung T(RM)pool is also sustained by continual replenishment from circulating memory CD8 T cells that differentiate into lung T-RM, 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.

Automated summary

The study demonstrates that lung tissue-resident memory T cells (T-RM) can be maintained for at least a year post vaccination with an adenovirus expressing influenza nucleoprotein. The lung T-RM cells continued to proliferate in situ 8 months after vaccination, requiring airway vaccination and antigen persistence in the lung for long-term maintenance. Additionally, the lung T-RM pool is sustained by continual replenishment from circulating memory CD8 T cells in vaccinated mice.