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

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.

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.).

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

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

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

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

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

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

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

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

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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