Stored Fas ligand, a mediator of rapid CTL-mediated killing, has a lower threshold for response than degranulation or newly synthesized Fas ligand

The Journal of Immunology : Official Journal of the American Association of Immunologists
Jin-Shu HeHanne L Ostergaard

Abstract

CTL lyse target cells through the release of cytolytic granule mediators and expression of the death receptor ligand Fas ligand (FasL). We previously demonstrated that FasL is stored in vesicles distinct from cytolytic granules and is translocated to the cell surface within 15 min of TCR stimulation, followed by a later wave of newly synthesized FasL cell surface expression at 2 h poststimulation. Initial studies suggested that the two FasL responses had different signaling thresholds. To test this possibility directly, we titrated Ag presented to murine CTL to measure FasL and degranulation response thresholds. Stored FasL translocation to the cell surface required substantially lower concentrations of peptide than was required for de novo expression of FasL and degranulation. Furthermore, a low-affinity agonist peptide stimulated strong stored FasL translocation but only limited de novo FasL expression and degranulation. These data imply that the two FasL populations may have distinct functions. We examined bystander killing and found that the rapidly expressed FasL triggered highly specific lysis of target cells, as did degranulation. In contrast, the newly synthesized later wave of FasL mediated extensive Fas-dependent byst...Continue Reading

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Citations

Jul 16, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Govindarajan ThangaveluColin C Anderson
Jul 3, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amy V PaschallKebin Liu
Oct 19, 2016·European Journal of Immunology·Jennifer L Gardell, David C Parker
Jun 30, 2015·Scandinavian Journal of Immunology·M LettauO Janssen
Jun 17, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yoshinobu KoguchiDavid C Parker
Jul 13, 2021·Frontiers in Immunology·Jie ZhuBin Qu
Dec 4, 2010·European Journal of Cell Biology·Marcus LettauOttmar Janssen

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