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

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

Content Provider	Scilit
Author	Prager, Isabel Liesche, Clarissa Ooijen, Hanna Van Urlaub, Doris Verron, Quentin Sandström, Niklas Fasbender, Frank Claus, Maren Eils, Roland Beaudouin, Joël Önfelt, Björn Watzl, Carsten
Copyright Year	2019
Description	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.
Related Links	https://rupress.org/jem/article-pdf/216/9/2113/871312/jem_20181454.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6719417/pdf https://rupress.org/jem/article-pdf/216/9/2113/847075/jem_20181454.pdf
Ending Page	2127
Page Count	15
Starting Page	2113
DOI	10.1084/jem.20181454
Journal	The Journal of experimental medicine
Issue Number	9
Volume Number	216
Language	English
Publisher	Rockefeller University Press
Publisher Date	2019-09-02
Access Restriction	Open
Subject Keyword	Research and Experimental Medicine Cell Death Nk Cells Switch Death Receptor Serial Killing Mediated Differentially Grzb Journal: The Journal of experimental medicine (Vol- 216, Issue- 9)
Content Type	Text

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