Licensing delineates helper and effector NK cell subsets during viral infection

Anthony E. Zamora, Ethan G. Aguilar, Can M. Sungur, Lam T. Khuat, Cordelia Dunai, G. Raymond Lochhead, Juan Du, Claire Pomeroy, Bruce R. Blazar, Dan L. Longo, Jeffrey M. Venstrom, Nicole Baumgarth, William J. Murphy

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


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.

Original languageEnglish (US)
Article numbere87032
JournalJCI Insight
Issue number10
StatePublished - May 18 2017

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© 2017 American Society for Clinical Investigation. All rights reserved.


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