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2018 ; 128
(2
): 721-733
Nephropedia Template TP
gab.com Text
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English Wikipedia
Influenza-specific lung-resident memory T cells are proliferative and
polyfunctional and maintain diverse TCR profiles
#MMPMID29309047
Pizzolla A
; Nguyen TH
; Sant S
; Jaffar J
; Loudovaris T
; Mannering SI
; Thomas PG
; Westall GP
; Kedzierska K
; Wakim LM
J Clin Invest
2018[Feb]; 128
(2
): 721-733
PMID29309047
show ga
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.