TY - JOUR
T1 - Classification of human natural killer cells based on migration behavior and cytotoxic response
AU - Vanherberghen, Bruno
AU - Olofsson, Per E.
AU - Forslund, Elin
AU - Sternberg-Simon, Michal
AU - Khorshidi, Mohammad Ali
AU - Pacouret, Simon
AU - Guldevall, Karolin
AU - Enqvist, Monika
AU - Malmberg, Karl Johan
AU - Mehr, Ramit
AU - Önfelt, Björn
PY - 2013/2/21
Y1 - 2013/2/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84874447340&partnerID=8YFLogxK
U2 - 10.1182/blood-2012-06-439851
DO - 10.1182/blood-2012-06-439851
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C2 - 23287857
AN - SCOPUS:84874447340
SN - 0006-4971
VL - 121
SP - 1326
EP - 1334
JO - Blood
JF - Blood
IS - 8
ER -