Licensing delineates helper and effector NK cell subsets during viral infection

JCI Insight
Anthony E ZamoraWilliam J Murphy

Abstract

Natural killer (NK) cells can be divided into phenotypic subsets based on expression of receptors that bind self-MHC-I molecules, a concept termed licensing or education. Here we show NK cell subsets with different migratory, effector, and immunoregulatory functions in dendritic cell and antigen (ag)-specific CD8+ T cell responses during influenza and murine cytomegalovirus infections. Shortly after infection, unlicensed NK cells localized in draining lymph nodes and produced GM-CSF, which correlated with the expansion and activation of dendritic cells, and resulted in greater and sustained ag-specific T cell responses. In contrast, licensed NK cells preferentially migrated to infected tissues and produced IFN-γ. Importantly, human NK cell subsets exhibited similar phenotypic characteristics. Collectively, our studies demonstrate a critical demarcation between the functions of licensed and unlicensed NK cell subsets, with the former functioning as the classical effector subset and the latter as the stimulator of adaptive immunity helping to prime immune responses.

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Citations

Dec 14, 2017·Archivum Immunologiae Et Therapiae Experimentalis·Danuta NowickaJacek Roliński
Oct 17, 2019·International Journal of Molecular Sciences·Paola FisicaroCarolina Boni
Dec 18, 2019·Proceedings of the National Academy of Sciences of the United States of America·Awndre GamacheMichael G Brown
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Mar 17, 2019·Current Opinion in Virology·Ayad AliStephen N Waggoner

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Datasets Mentioned

BETA
GSE72632

Methods Mentioned

BETA
flow cytometry
genotyping
PCR
density

Software Mentioned

Tree Star
DAVID
FlowJo

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