Title: Influenza-specific lung-resident memory T cells are proliferative and polyfunctional and maintain diverse TCR profiles
Authors: Pizzolla, A
Nguyen, THO
Sant, S
Jaffar, J
Loudovaris, T
Mannering, SI
Thomas, PG
Westall, GP
Kedzierska, K
Wakim, LM
Issue Year: 2018
Series J. Clin. Invest.:
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.
URI: https://publications.svi.edu.au/publications/4629
Other Identifiers 10.1172/JCI96957
Publication type Article