Journal
NATURE IMMUNOLOGY
Volume 10, Issue 7, Pages 761-U121Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.1757
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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.
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