Therapeutic effect of an anti-Fas ligand mAb on lethal graft-versus-host disease

Several anti-fas ligand (FasL) inhibitory mAb (FLIM) were raised and charac terized in this study. One, FLIM58, showed more potent neutralizing activit y than Fas-Fc, the previously established artificial neutralizing agent for Fast. Several murine models of acute graft-versus-host disease (GVHD) afte r allogeneic bone marrow transplantation have been used to show that both F ast and perforin, the major effector molecules of cytotoxic T lymphocytes, are involved in this disease. In our GVHD model, Fast rather than perforin was associated with lethality. Administration of FLIM58 or Fas-Fc reduced t he weight loss and mortality caused by GVHD, although other signs of GVHD, such as skin lesions, lymphoid hypoplasia and mononuclear cell infiltration in the liver did not improve significantly. FLIM58 was more effective than Fas-Fc in reducing mortality. Our results demonstrated that neutralizing a gents for Fast are therapeutic for lethal GVHD.