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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
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
-
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
-
fas Receptor / metabolism*
-
fas Receptor / toxicity
Substances
-
Apoptosis Regulatory Proteins
-
FASLG protein, human
-
Fas Ligand Protein
-
Ligands
-
Membrane Glycoproteins
-
Phytohemagglutinins
-
TNF-Related Apoptosis-Inducing Ligand
-
TNFSF10 protein, human
-
Tumor Necrosis Factor-alpha
-
fas Receptor
-
Cytochalasin B
-
Endopeptidases