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 journalArticle

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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.

Original languageEnglish (US)
JournalJCI insight
Volume2
Issue number10
DOIs
StatePublished - May 18 2017

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Virus Diseases
Licensure
Natural Killer Cells
Dendritic Cells
Muromegalovirus
CD8 Antigens
T-Lymphocytes
Cytomegalovirus Infections
Adaptive Immunity
Granulocyte-Macrophage Colony-Stimulating Factor
Human Influenza
Lymph Nodes
Education
Antigens
Infection

Keywords

  • Immunology
  • Inflammation

Cite this

Zamora, A. E., Aguilar, E. G., Sungur, C. M., Khuat, L. T., Dunai, C., Lochhead, G. R., ... Murphy, W. J. (2017). Licensing delineates helper and effector NK cell subsets during viral infection. JCI insight, 2(10). https://doi.org/10.1172/jci.insight.87032

Licensing delineates helper and effector NK cell subsets during viral infection. / Zamora, Anthony E.; Aguilar, Ethan G.; Sungur, Can M.; Khuat, Lam T.; Dunai, Cordelia; Lochhead, G. Raymond; Du, Juan; Pomeroy, Claire; Blazar, Bruce R.; Longo, Dan L.; Venstrom, Jeffrey M.; Baumgarth, Nicole; Murphy, William J.

In: JCI insight, Vol. 2, No. 10, 18.05.2017.

Research output: Contribution to journalArticle

Zamora, AE, Aguilar, EG, Sungur, CM, Khuat, LT, Dunai, C, Lochhead, GR, Du, J, Pomeroy, C, Blazar, BR, Longo, DL, Venstrom, JM, Baumgarth, N & Murphy, WJ 2017, 'Licensing delineates helper and effector NK cell subsets during viral infection', JCI insight, vol. 2, no. 10. https://doi.org/10.1172/jci.insight.87032
Zamora AE, Aguilar EG, Sungur CM, Khuat LT, Dunai C, Lochhead GR et al. Licensing delineates helper and effector NK cell subsets during viral infection. JCI insight. 2017 May 18;2(10). https://doi.org/10.1172/jci.insight.87032
Zamora, Anthony E. ; Aguilar, Ethan G. ; Sungur, Can M. ; Khuat, Lam T. ; Dunai, Cordelia ; Lochhead, G. Raymond ; Du, Juan ; Pomeroy, Claire ; Blazar, Bruce R. ; Longo, Dan L. ; Venstrom, Jeffrey M. ; Baumgarth, Nicole ; Murphy, William J. / Licensing delineates helper and effector NK cell subsets during viral infection. In: JCI insight. 2017 ; Vol. 2, No. 10.
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