Abstract
We and others have recently shown that human NK cells express the Fas ligand (FasL) constitutively and that they can trigger the lysis of Fas positive (Fas+) target cells (TC) by apoptosis. We have also previously demonstrated that NK cells exposed to sensitive TC temporarily lose their ability to lyse sensitive TC via the granule-mediated pathway and that this loss is recovered when inactivated NK cells (NKi) are incubated in medium supplemented with IL-2, IL-12 or IL-15. In this study, we investigated the fate of the Fas-lytic pathway in NK cells exposed to either Fas+ or Fas− TC. To this end, we exposed NK cells to Jurkat (Fas−) or Jurkat (Fas+) TC for up to 6 h, separated NK cells from the TC and assessed the residual lytic activity against K562, a traditional human NK cell target, Jurkat Fas+ and Jurkat Fas− TC. Fas lytic activity was determined in calcium free medium, in the presence or absence of two distinct Fas-blocking monoclonal antibodies and a Fas.Fc fusion protein. In parallel experiments, the extent of DNA fragmentation in the three TCs was also assayed by the JAM test. Our results indicate that: (i) NK cells exposed to susceptible Fas+ TC temporarily lose most of their lytic potential due to the granule-mediated pathway, while only partially losing the Fas-lytic pathway. They also partially lose their ability to fragment DNA. (ii) NK cells exposed to Fas+ TC completely recover the Fas lytic pathway and the ability to fragment DNA via the Fas/Fas ligand when incubated in medium supplemented with IL-2 for 18 h.
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Csipo, I., Montel, A.H., Hobbs, J.A. et al. Effect of Fas+ and Fas− Target Cells on the Ability of NK Cells to Repeatedly Fragment DNA and Trigger Lysis via the Fas Lytic Pathway. Apoptosis 3, 105–114 (1998). https://doi.org/10.1023/A:1009696908600
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DOI: https://doi.org/10.1023/A:1009696908600