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Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias,
Servicio de Inmunología, Hospital Clínico Universitario, and
Departamento de Anatomía, Embriología y Genética, Facultad de Veterinaria, Universidad de Zaragoza, Zaragoza, Spain; and
Serveis Científico-Tècnics, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain
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
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.
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