REQUIREMENT OF CELL-CELL CONTACT IN THE INDUCTION OF JURKAT T-CELL APOPTOSIS - THE MEMBRANE-ANCHORED BUT NOT SOLUBLE FORM OF FASL CAN TRIGGER ANTI-CD3-INDUCED APOPTOSIS IN JURKAT T-CELLS

Fas ligand (Fast) has been shown to be processed by the action of cert ain metalloproteinase and released from the cell surface, However, it is unclear whether death of Fas-sensitive target cells is mediated by a membrane-bound form of Fast (mFasL) or by a soluble form of Fast (sF asL), In the present study, we demonstrated that JCaM, a p56lck-defici ent mutant of Jurkat, underwent Fas dependent apoptosis only upon phys ical contact with anti-CD3-stimulated Jurkat cells or with human Fast- expressing transfectant (hFas/L5178Y). Recombinant Fast or sFasL-conta ining supernatant failed to induce apoptosis in both Jurkat and JCaM. Moreover, addition of a metalloproteinase inhibitor, which led to the accumulation of mFasL in hFas/L5178Y, was found to augment apoptosis i n both Jurkat and JCaM. These findings indicate that, in a physiologic setting represented by the activation-induced cell death in Jurkat T cells, cell-cell contact appears to be required for the induction of F as-mediated killing. (C) 1997 Academic Press.