A MAJOR ROLE FOR THE FAS PATHWAY IN ACUTE GRAFT-VERSUS-HOST DISEASE

Recent studies have suggested a role for the Fas pathway in the wastin g syndrome associated with lpr-->wild-type bone marrow transplants. To directly examine whether Fas ligand has a major role in the developme nt of acute graft-vs-host disease (GVHD), Fas ligand-deficient (gld) m ice were used as donors and C3H/HeJ x C57BL/6F(1) as recipients in the parent-into-F-1 model of acute GVHD, Transplantation of C3H/gld splee n cells induced significantly less host lymphoid depletion and was ass ociated with less antihost cytotoxic activity in vitro when compared w ith wild-type C3H donor cells. The reduced depletion of host lymphocyt es was explained by both impaired antihost T cell cytolytic activity a nd by reduced expansion of gld donor T cells in F-1 recipients, These findings not only indicate that the Fas ligand is an important effecto r molecule in acute GVHD, but also provide in vivo evidence supporting a role for Fas/Fas ligand interactions in T cell expansion and matura tion.