Activated human T cells release bioactive Fas ligand and APO2 ligand in microvesicles.
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.
Departamento de Bioquímica y Biología Molecular y Cellular, Facultad de Ciencias, Servicio de Inmunología, Hospital Clínico Universitario, Universidad de Zaragoza, Spain.
M J
MJ
Martínez-Lorenzo
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A
Anel
S
S
Gamen
I
I
Monle n
P
P
Lasierra
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L
Larrad
A
A
Piñeiro
M A
MA
Alava
J
J
Naval
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins; D002474:Cell-Free System / Q000737:chemistry / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D003571:Cytochalasin B / Q000494:pharmacology; D010450:Endopeptidases; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D006801:Humans; D006868:Hydrolysis; D019169:Jurkat Cells; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000633:toxicity; D017348:Microscopy, Electron, Scanning Transmission; D008969:Molecular Sequence Data; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism* / Q000648:ultrastructure; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000633:toxicity; D014461:Ultracentrifugation; D014617:Vacuoles / Q000737:chemistry / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D019014:fas Receptor / Q000378:metabolism* / Q000633:toxicity
D051017:Apoptosis Regulatory Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D010835:Phytohemagglutinins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D003571:Cytochalasin B; D010450:Endopeptidases