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

作者：Herz Jasmin; Pardo Julian; Kashkar Hamid; Schramm Michael; Kuzmenkina Elza; Bos Erik; Wiegmann Katja; Wallich Reinhard; Peters Peter J; Herzig Stefan; Schmelzer Elmon; Kroenke Martin; Simon Markus M; Utermoehlen Olaf

来源：Nature Immunology, 2009, 10(7): 761-U121.

DOI：10.1038/ni.1757

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.

• 出版日期2009-7
• 单位河北医科大学