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

22 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

Bibliographical note

Funding Information:
We would to thank Weihong Ma, Monja Metcalf, and Yajarayma Tang-Feldman for their technical help. We would also like to thank the other members in the Murphy lab for providing feedback and suggestions during preparation of the manuscript. We would also like to acknowledge the UC Davis Comprehensive Cancer Center’s Genomics Shared Resource core facility for their help with performing and analyzing the microarray data. The UC Davis Comprehensive Cancer Center Genomics Shared Resource is supported by Cancer Center Support Grant P30 CA093373 from the National Cancer Institute (NCI). We would also like to thank the NIH tetramer core facility at Emory University for providing the tetramers utilized in the studies. This work was funded by NIH grants R01 HL08990 and R01 CA72669. This project has been funded in whole or in part with federal funds from the NCI, NIH, under contract HHSN26120080001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported in part by the Intramural Research Program of the NIH, NCI, Center for Cancer Research.

Publisher Copyright:
© 2017 American Society for Clinical Investigation. All rights reserved.


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