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Sökning: id:"swepub:oai:DiVA.org:kth-256334" > NK cells switch fro...

NK cells switch from granzyme B to death receptor–mediated cytotoxicity during serial killing

Prager, Isabel (författare)
Department for Immunology, Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund, Dortmund, Germany
Liesche, Clarissa (författare)
Division of Theoretical Bioinformatics, German Cancer Research Center and BioQuant Center, Heidelberg, Germany
van Ooijen, Hanna (författare)
KTH,Biofysik,Science for Life Laboratory, SciLifeLab
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Urlaub, Doris (författare)
Department for Immunology, Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund, Dortmund, Germany
Verron, Quentin (författare)
KTH,Biofysik,Science for Life Laboratory, SciLifeLab
Sandström, Niklas, 1981- (författare)
KTH,Biofysik,Science for Life Laboratory, SciLifeLab,Önfelt Lab
Fasbender, Frank (författare)
Department for Immunology, Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund, Dortmund, Germany
Claus, Maren (författare)
Department for Immunology, Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund, Dortmund, Germany
Eils, Roland (författare)
Division of Theoretical Bioinformatics, German Cancer Research Center and BioQuant Center, Heidelberg, Germany
Beaudouin, Joël (författare)
Division of Theoretical Bioinformatics, German Cancer Research Center and BioQuant Center, Heidelberg, Germany
Önfelt, Björn (författare)
KTH,Biomedicinsk fysik och röntgenfysik,Science for Life Laboratory, SciLifeLab
Watzl, Carsten (författare)
Department for Immunology, Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund, Dortmund, Germany
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 (creator_code:org_t)
2019-07-03
2019
Engelska.
Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 7:9, s. 2113-2127
Relaterad länk:
https://rupress.org/...
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https://urn.kb.se/re...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • NK cells eliminate virus-infected and tumor cells by releasing cytotoxic granules containing granzyme B (GrzB) or by engaging death receptors that initiate caspase cascades. The orchestrated interplay between both cell death pathways remains poorly defined. Here we simultaneously measure the activities of GrzB and caspase-8 in tumor cells upon contact with human NK cells. We observed that NK cells switch from inducing a fast GrzB-mediated cell death in their first killing events to a slow death receptor–mediated killing during subsequent tumor cell encounters. Target cell contact reduced intracellular GrzB and perforin and increased surface-CD95L in NK cells over time, showing how the switch in cytotoxicity pathways is controlled. Without perforin, NK cells were unable to perform GrzB-mediated serial killing and only killed once via death receptors. In contrast, the absence of CD95 on tumor targets did not impair GrzB-mediated serial killing. This demonstrates that GrzB and death receptor–mediated cytotoxicity are differentially regulated during NK cell serial killing.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

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