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Acid sphingomyelinase is a key regulator of cytotoxic granule secretion by primary T lymphocytes

Granule-mediated cytotoxicity is the main effector mechanism of cytotoxic CD8+ T cells. We report that CD8+ T cells from acid sphingomyelinase (ASMase)-deficient (ASMase-KO) mice are defective in exocytosis of cytolytic effector molecules; this defect resulted in attenuated cytotoxic activity of ASM...

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Main Authors: Herz, Jasmin (Author) , Pardo, Julian (Author) , Kashkar, Hamid (Author) , Schramm, Michael (Author) , Kuzmenkina, Elza (Author) , Bos, Erik (Author) , Wiegmann, Katja (Author) , Wallich, Reinhard (Author) , Peters, Peter J. (Author) , Herzig, Stefan (Author) , Schmelzer, Elmon (Author) , Krönke, Martin (Author) , Simon, Markus M. (Author) , Utermöhlen, Olaf (Author)
Format: Article (Journal)
Language:English
Published: 14 June 2009
In: Nature immunology
Year: 2009, Volume: 10, Issue: 7, Pages: 761-768
ISSN:1529-2916
DOI:10.1038/ni.1757
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/ni.1757
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/ni.1757
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Author Notes:Jasmin Herz, Julian Pardo, Hamid Kashkar, Michael Schramm, Elza Kuzmenkina, Erik Bos, Katja Wiegmann, Reinhard Wallich, Peter J. Peters, Stefan Herzig, Elmon Schmelzer, Martin Krönke, Markus M. Simon & Olaf Utermöhlen
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Summary:Granule-mediated cytotoxicity is the main effector mechanism of cytotoxic CD8+ T cells. We report that CD8+ T cells from acid sphingomyelinase (ASMase)-deficient (ASMase-KO) mice are defective in exocytosis of cytolytic effector molecules; this defect resulted in attenuated cytotoxic activity of ASMase-KO CD8+ T cells and delayed elimination of lymphocytic choriomeningitis virus from ASMase-KO mice. Cytolytic granules of ASMase-KO and wild-type CD8+ T cells were equally loaded with granzymes and perforin, and correctly directed to the immunological synapse. In wild-type CD8+ T cells, secretory granules underwent shrinkage by 82% after fusion with the plasma membrane. In ASMase-KO CD8+ T cells, the contraction of secretory granules was markedly impaired. Thus, ASMase is required for contraction of secretory granules and expulsion of cytotoxic effector molecules.
Item Description:Gesehen am 17.05.2021
Physical Description:Online Resource
ISSN:1529-2916
DOI:10.1038/ni.1757

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