Activated human T cells release bioactive Fas ligand and APO2 ligand in microvesicles

Activation-induced cell death is a process by which overactivated T cells a re eliminated, thus preventing potential autoimmune attacks. Two known medi ators 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 Fast and APO2L are released fro m 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 n m in diameter. These microvesicles are released from Jurkat and T cell blas ts shortly (less than or equal to 1 h) after PHA stimulation, well before t he cell enters apoptosis, FasL- and APO2L-containing vesicles are also pres ent in supernatants from PHA-activated fresh human PBMC, These observations provide the basis for a new and efficient mechanism for the rapid inductio n of autocrine or paracrine cell death during immune regulation.