Activated human T cells release bioactive Fas ligand and APO2 ligand in microvesicles. |
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Authors: | M J Martínez-Lorenzo A Anel S Gamen I Monle n P Lasierra L Larrad A Pi?eiro M A Alava J Naval |
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Affiliation: | Departamento de Bioquímica y Biología Molecular y Cellular, Facultad de Ciencias, Servicio de Inmunología, Hospital Clínico Universitario, Universidad de Zaragoza, Spain. |
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Abstract: | Activation-induced cell death is a process by which overactivated T cells are eliminated, thus preventing potential autoimmune attacks. Two known mediators of activation-induced cell death are Fas(CD95) ligand (FasL) and APO2 ligand (APO2L)/TNF-related apoptosis-inducing ligand (TRAIL). We show here that upon mitogenic stimulation, bioactive FasL and APO2L are released from the T cell leukemia Jurkat and from normal human T cell blasts as intact, nonproteolyzed proteins associated with a particulate, ultracentrifugable fraction. We have characterized this fraction as microvesicles of 100-200 nm in diameter. These microvesicles are released from Jurkat and T cell blasts shortly (=1 h) after PHA stimulation, well before the cell enters apoptosis. FasL- and APO2L-containing vesicles are also present in supernatants from PHA-activated fresh human PBMC. These observations provide the basis for a new and efficient mechanism for the rapid induction of autocrine or paracrine cell death during immune regulation. |
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