title: 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.
abstract: Fas ligand (FasL) has been shown to be processed by the action of certain 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 FasL (mFasL) or by a soluble form of FasL (sFasL). In the present study, we demonstrated that JCaM, a p56lck-deficient mutant of Jurkat, underwent Fas-dependent apoptosis only upon physical contact with anti-CD3-stimulated Jurkat cells or with human FasL- expressing transfectant (hFas/L5178Y). Recombinant FasL or sFasL-containing 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 in 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 Fas-mediated killing.
authors.affiliation: Department of Retroviral Regulation, Tokyo Medical Dental University, Tokyo, 113, Japan. oyaizu.mbch@med.tmd.ac.jp
authors.forename: N
authors.initials: N
authors.lastname: Oyaizu
authors.forename: N
authors.initials: N
authors.lastname: Kayagaki
authors.forename: H
authors.initials: H
authors.lastname: Yagita
authors.forename: S
authors.initials: S
authors.lastname: Pahwa
authors.forename: Y
authors.initials: Y
authors.lastname: Ikawa
mesh_terms: D017209:Apoptosis / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D053222:Fas Ligand Protein; D006801:Humans; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*
chemical_list: D017252:CD3 Complex; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins