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JCI Insight. 2017 May 18;2(10). pii: 87032. doi: 10.1172/jci.insight.87032. [Epub ahead of print]
Licensing delineates helper and effector NK cell subsets during viral infection.
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.
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.
PMID: 28515356 DOI: 10.1172/jci.insight.87032
Free full text
Licensing delineates helper and effector NK cell subsets during viral infection.
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.
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.
PMID: 28515356 DOI: 10.1172/jci.insight.87032
Free full text