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.