@article{668842aaf098441cb02d331b3e0b61c6,
title = "Acid sphingomyelinase is a key regulator of cytotoxic granule secretion by primary T lymphocytes",
abstract = "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.",
author = "Jasmin Herz and Julian Pardo and Hamid Kashkar and Michael Schramm and Elza Kuzmenkina and Erik Bos and Katja Wiegmann and Reinhard Wallich and Peters, \{Peter J.\} and Stefan Herzig and Elmon Schmelzer and Martin Kr{\"o}nke and Simon, \{Markus M.\} and Olaf Uterm{\"o}hlen",
note = "Funding Information: We thank R. Kolesnick (Memorial Sloan-Kettering Cancer Center) and D.R. Green and T. Lin (La Jolla Institute for Allergy and Immunology) for ASMase-KO mice; H. Hengartner (Institute for Experimental Immunology, University Hospital Z{\"u}rich) for perforin-deficient mice; U. Karow, A. Ekiciler and B. Hub for expert technical assistance; and E.-M. Menke, D. We≈ler and J. van de Burgwal for expert work at the animal facility. Supported by the Deutsche Forschungsgemeinschaft (SFB 670 and SPP1110 to O.U. and M.K.), an Alexander von Humboldt foundation fellowship (J.P.), Fundacion Aragon I+D (J.P.) and the Christiane N{\"u}sslein-Volhard Foundation (E.K.).",
year = "2009",
doi = "10.1038/ni.1757",
language = "English",
volume = "10",
pages = "761--768",
journal = "Nature immunology",
issn = "1529-2908",
number = "7",
}