Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways (original) (raw)

Nature volume 370, pages 650–652 (1994)Cite this article

Abstract

THE recent generation of perform knock-out mice1,2 has demonstrated a crucial role for the pore-forming perforin in cytolytic T-lymphocyte (CTL)-mediated cytolysis. Perforin-deficient mice failed to clear lymphocytic choriomeningitis virus in vivo, yet substantial killing activity still remained in perforin-free CTLs in vitro, indicating the presence of (a) further lytic pathway(s). Fas is an apoptosis-signalling receptor molecule on the surface of a number of different cells. Here we report that both perforin-deficient and Fas-ligand-deficient CTLs show impaired lytic activity on all target cells tested. The killing activity was completely abolished when both pathways were inactivated by using target cells from Fas-receptor-deficient lpr mice and perforin-free CTL effector cells. Fas-ligand-based killing activity was triggered upon T-cell receptor occupancy and was directed to the cognate target cell. Thus, two complementary, specific cytotoxic mechanisms are functional in CTLs, one based on the secretion of lytic proteins and one which depends on cell-surface ligand–receptor interaction.

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Authors and Affiliations

  1. Institute of Biochemistry, University of Lausanne, CH-1066, Epalinges, Switzerland
    Bente Lowin, Michael Hahne, Chantal Mattmann & Jürg Tschopp

Authors

  1. Bente Lowin
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  2. Michael Hahne
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  3. Chantal Mattmann
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  4. Jürg Tschopp
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Lowin, B., Hahne, M., Mattmann, C. et al. Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways.Nature 370, 650–652 (1994). https://doi.org/10.1038/370650a0

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