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-i nducing ligand (TRAIL) are stored in the cytoplasm of the human Jurkat T ce ll line and of normal human T cell blasts. The rapid release of these molec ules 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 al so by immunoelectron microscopy that FasL and APO2L/TRAIL are stored inside cytoplasmic compartments similar to 500 nm in diameter, with characteristi cs of multivesicular bodies. Most of these compartments share FasL and APO2 L/TRAIL, although exclusive APO2L/TRAIL labeling can be also observed in se parate compartments. Upon PRA activation, the mobilization of these compart ments 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 pref erentially with APO2L/TRAIL predominates. These data provide the basis of a new and efficient mechanism for the rapid induction of autocrine or paracr ine cell death during immune regulation and could modify the interpretation of the role of FasL and APO2L/TRAIL as effector mechanisms in physiologica l and pathological situations.