Classification of human natural killer cells based on migration behavior and cytotoxic response

Bruno Vanherberghen, Per E. Olofsson, Elin Forslund, Michal Sternberg-Simon, Mohammad Ali Khorshidi, Simon Pacouret, Karolin Guldevall, Monika Enqvist, Karl-Johan Malmberg, Ramit Mehr and Björn Önfelt

Key points

  • Activated NK cells display heterogeneity in their cytotoxic responses justifying grouping into five distinct classes of NK cells

  • A subpopulation of particularly active serial killer NK cells deliver their lytic hits faster and release more perforin in each hit


Despite intense scrutiny of the molecular interactions between natural killer (NK) and target cells, few studies have been devoted to dissection of basic functional heterogeneity in individual NK cell behavior. By using a microchip-based, time-lapse imaging approach allowing the entire contact history of each NK cell to be recorded, we could quantify how the cytotoxic response varies between individual NK cells. Strikingly, about half of the NK cells did not kill any target cells at all, while a minority of NK cells was responsible for a majority of the target cell deaths. These dynamic cytotoxicity data allowed categorization of NK cells into five distinct classes. A small but particularly active sub-class of NK cells killed several target cells in a consecutive fashion. These 'serial killers' delivered their lytic hits faster and induced faster target cell death than other NK cells. Fast, necrotic target cell death was correlated with the amount of perforin released by the NK cells. Our data are consistent with a model where a small fraction of NK cells drives tumor elimination and inflammation.

  • Submitted June 28, 2012.
  • Accepted December 3, 2012.