title: Classification of human natural killer cells based on migration behavior and cytotoxic response.
abstract: Despite intense scrutiny of the molecular interactions between natural killer (NK) and target cells, few studies have been devoted to dissection of the basic functional heterogeneity in individual NK cell behavior. Using a microchip-based, time-lapse imaging approach allowing the entire contact history of each NK cell to be recorded, in the present study, we were able to quantify how the cytotoxic response varied between individual NK cells. Strikingly, approximately half of the NK cells did not kill any target cells at all, whereas 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 5 distinct classes. A small but particularly active subclass 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 in which a small fraction of NK cells drives tumor elimination and inflammation.
authors.affiliation: Department of Applied Physics, Albanova University Center, KTH Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vanherberghen
authors.forename: Per E
authors.initials: PE
authors.lastname: Olofsson
authors.forename: Elin
authors.initials: E
authors.lastname: Forslund
authors.forename: Michal
authors.initials: M
authors.lastname: Sternberg-Simon
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Khorshidi
authors.forename: Simon
authors.initials: S
authors.lastname: Pacouret
authors.forename: Karolin
authors.initials: K
authors.lastname: Guldevall
authors.forename: Monika
authors.initials: M
authors.lastname: Enqvist
authors.forename: Karl-Johan
authors.initials: KJ
authors.lastname: Malmberg
authors.forename: Ramit
authors.initials: R
authors.lastname: Mehr
authors.forename: Björn
authors.initials: B
authors.lastname: Önfelt
mesh_terms: D017209:Apoptosis / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D015550:Cell Degranulation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D057809:HEK293 Cells; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000145:classification* / Q000166:cytology* / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D046208:Microchip Analytical Procedures; D008954:Models, Biological; D009336:Necrosis / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification* / Q000166:cytology* / Q000276:immunology; D059008:Time-Lapse Imaging