期刊
INTEGRATIVE BIOLOGY
卷 5, 期 4, 页码 712-719出版社
OXFORD UNIV PRESS
DOI: 10.1039/c3ib20253d
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资金
- Swedish Foundation for Strategic Research
- Swedish Research Council
- Goran Gustafsson Foundation
- Jeansson Foundation
- Clas Groschinsky Foundation
- Ake Wiberg Foundation
Natural killer (NK) cells kill virus-infected or cancer cells through the release of cytotoxic granules into a tight intercellular contact. NK cell populations comprise individual cells with varying sensitivity to distinct input signals, leading to disparate responses. To resolve this NK cell heterogeneity, we have designed a novel assay based on ultrasound-assisted cell-cell aggregation in a multiwell chip allowing high-resolution time-lapse imaging of one hundred NK-target cell interactions in parallel. Studying human NK cells' ability to kill MHC class I deficient tumor cells, we show that approximately two thirds of the NK cells display cytotoxicity, with some NK cells being particularly active, killing up to six target cells during the assay. We also report that simultaneous interaction with several susceptible target cells increases the cytotoxic responsiveness of NK cells, which could be coupled to a previously unknown regulatory mechanism with implications for NK-mediated tumor elimination.
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