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Critical role for the chemokine receptor CXCR6 in NK cell–mediated antigen-specific memory of haptens and viruses

Nature Immunology volume 11, pages 1127–1135 (2010)Cite this article

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Abstract

Hepatic natural killer (NK) cells mediate antigen-specific contact hypersensitivity (CHS) in mice deficient in T cells and B cells. We report here that hepatic NK cells, but not splenic or naive NK cells, also developed specific memory of vaccines containing antigens from influenza, vesicular stomatitis virus (VSV) or human immunodeficiency virus type 1 (HIV-1). Adoptive transfer of virus-sensitized NK cells into naive recipient mice enhanced the survival of the mice after lethal challenge with the sensitizing virus but not after lethal challenge with a different virus. NK cell memory of haptens and viruses depended on CXCR6, a chemokine receptor on hepatic NK cells that was required for the persistence of memory NK cells but not for antigen recognition. Thus, hepatic NK cells can develop adaptive immunity to structurally diverse antigens, an activity that requires NK cell–expressed CXCR6.

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Figure 1: Liver NK cells develop specific memory of haptens.
Figure 2: Liver NK cells develop specific memory of viral antigens.
Figure 3: Mouse liver NK cells recognize and discriminate between HIV-1 and influenza A.
Figure 4: NK cell–expressed CXCR6 is required for NK cell–mediated adaptive immunity to haptens.
Figure 5: NK cell–expressed CXCR6 is required for NK cell–mediated adaptive immunity to viruses.
Figure 6: CXCR6 regulates hepatic NK cell homeostasis.
Figure 7: Hepatic memory NK cells mediate hapten-specific killing in vitro.

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Acknowledgements

We thank G. Cheng and J.D. Sullivan for technical support and A. Wagers (Harvard Medical School) for Act(EGFP) mice. Supported by the US National Institutes of Health (AI069259, AI072252, AI078897, HL56949 and AR42689), the Ragon Institute (U.H.v.A.), the Cancer Research Institute (S.P.) and the Ragon Institute of MIT, Harvard and MGH (S.P.).

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Authors and Affiliations

  1. Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA

    Silke Paust, Michael P Flynn, E Ashley Moseman, Balimkiz Senman & Ulrich H von Andrian

  2. The Ragon Institute of MIT, MGH and Harvard, Charlestown, Massachusetts, USA

    Silke Paust & Amalio Telenti

  3. Department of Microbiology & Immunology and Emory Vaccine Center, Emory University, Atlanta, Georgia, USA

    Harvinder S Gill, Bao-Zhong Wang & Richard W Compans

  4. Department of Chemical Engineering, Texas Tech University, Lubbock, Texas, USA

    Harvinder S Gill

  5. Department of Human Developmental Biology, Jagiellonian University College of Medicine, Kraków, Poland

    Marian Szczepanik

  6. Institute of Microbiology, University Hospital, University of Lausanne, Lausanne, Switzerland

    Amalio Telenti

  7. Department of Medicine, Yale Medical School, New Haven, Connecticut, USA

    Marian Szczepanik & Philip W Askenase

  8. Immune Disease Institute, Boston, Massachusetts, USA

    Ulrich H von Andrian

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Contributions

S.P. and U.H.v.A. designed the study; S.P., H.S.G., B.Z.W. and M.F. did experiments; S.P., A.T. and B.S. collected and analyzed data; E.A.M., H.S.G., B.Z.W. and R.H.C. provided reagents; E.A.M., M.S. and P.W.A. provided technical support and conceptual advice; and S.P. and U.H.v.A. wrote the manuscript.

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Correspondence to Ulrich H von Andrian.

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Paust, S., Gill, H., Wang, BZ. et al. Critical role for the chemokine receptor CXCR6 in NK cell–mediated antigen-specific memory of haptens and viruses. Nat Immunol 11, 1127–1135 (2010). https://doi.org/10.1038/ni.1953

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