Differential Secretion of Fas Ligand- or APO2 Ligand/TNF-Related Apoptosis-Inducing Ligand-Carrying Microvesicles During Activation-Induced Death of Human T Cells

Preformed Fas ligand (FasL) and APO2 ligand (APO2L)/TNF-related apoptosis-inducing ligand (TRAIL) are stored in the cytoplasm of the human Jurkat T cell line and of normal human T cell blasts. The rapid release of these molecules in their bioactive form is involved in activation-induced cell death....

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Bibliographic Details
Published in:The Journal of immunology (1950) 2001-12, Vol.167 (12), p.6736-6744
Main Authors: Monleon, Inmaculada, Martinez-Lorenzo, Maria Jose, Monteagudo, Luis, Lasierra, Pilar, Taules, Marta, Iturralde, Maria, Pineiro, Andres, Larrad, Luis, Alava, Maria Angeles, Naval, Javier, Anel, Alberto
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal - pharmacology
APO2L protein
Apoptosis Regulatory Proteins
Biomarkers - analysis
CD59 Antigens - immunology
Cell Death
Cells, Cultured
Fas Ligand Protein
FasL protein
Flow Cytometry
Humans
Jurkat Cells
Lymphocyte Activation
Lysosomes - chemistry
Membrane Glycoproteins - metabolism
Microscopy, Confocal
Microscopy, Immunoelectron
microvesicles
Phytohemagglutinins - pharmacology
Secretory Vesicles - chemistry
Secretory Vesicles - ultrastructure
T-Lymphocytes - immunology
T-Lymphocytes - ultrastructure
TNF-Related Apoptosis-Inducing Ligand
TRAIL protein
Tumor Necrosis Factor-alpha - metabolism
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Summary:Preformed Fas ligand (FasL) and APO2 ligand (APO2L)/TNF-related apoptosis-inducing ligand (TRAIL) are stored in the cytoplasm of the human Jurkat T cell line and of normal human T cell blasts. The rapid release of these molecules in their bioactive form is involved in activation-induced cell death. In this study, we show by confocal microscopy that FasL and APO2L/TRAIL are mainly localized in lysosomal-like compartments in these cells. We show also by immunoelectron microscopy that FasL and APO2L/TRAIL are stored inside cytoplasmic compartments approximately 500 nm in diameter, with characteristics of multivesicular bodies. Most of these compartments share FasL and APO2L/TRAIL, although exclusive APO2L/TRAIL labeling can be also observed in separate compartments. Upon PHA activation, the mobilization of these compartments toward the plasma membrane is evident, resulting in the secretion of the internal microvesicles loaded with FasL and APO2L/TRAIL. In the case of activation with anti-CD59 mAb, the secretion of microvesicles labeled preferentially with APO2L/TRAIL predominates. These data provide the basis of a new and efficient mechanism for the rapid induction of autocrine or paracrine cell death during immune regulation and could modify the interpretation of the role of FasL and APO2L/TRAIL as effector mechanisms in physiological and pathological situations.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.167.12.6736