Activated Human T Cells Release Bioactive Fas Ligand and APO2 Ligand in Microvesicles

• Published in: The Journal of immunology (1950) Vol. 163; no. 3; pp. 1274 - 1281
• Main Authors: Martinez-Lorenzo, Maria Jose, Anel, Alberto, Gamen, Susana, Monleon, Inmaculada, Lasierra, Pilar, Larrad, Luis, Pineiro, Andres, Alava, Maria A, Naval, Javier
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01-08-1999
• Subjects: Amino Acid Sequence; Apoptosis - drug effects; Apoptosis - immunology; Apoptosis Regulatory Proteins; Cell-Free System - chemistry; Cell-Free System - immunology; Cell-Free System - metabolism; Cell-Free System - ultrastructure; Cytochalasin B - pharmacology; Endopeptidases; Fas Ligand Protein; fas Receptor - metabolism; fas Receptor - toxicity; Flow Cytometry; Humans; Hydrolysis; Jurkat Cells; Ligands; Lymphocyte Activation; Membrane Glycoproteins - antagonists & inhibitors; Membrane Glycoproteins - metabolism; Membrane Glycoproteins - toxicity; Microscopy, Electron, Scanning Transmission; Molecular Sequence Data; Phytohemagglutinins - pharmacology; T-Lymphocytes - chemistry; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes - ultrastructure; TNF-Related Apoptosis-Inducing Ligand; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - metabolism; Tumor Necrosis Factor-alpha - toxicity; Ultracentrifugation; Vacuoles - chemistry; Vacuoles - immunology; Vacuoles - metabolism; Vacuoles - ultrastructure
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.163.3.1274

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.