Critical role for CXCR6 in NK cell-mediated antigen-specific memory to haptens and viruses

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