Fas ligand-deficient gld mice are more susceptible to graft-versus-host-disease

Background. The Fas/Fas ligand (FasL) pathway plays an important role in a number of apoptotic processes that could be important for the development o f graft-versus-host disease (GVHD) after bone marrow transplantation (BMT), such as cytolysis of target cells by cytotoxic T cells, regulation of infl ammatory responses, peripheral deletion of autoimmune cells, costimulation of T cells, and activation-induced cell death. Methods. To study the role of the Fas/FasL pathway in the complex pathophys iology of graft versus host disease (GVHD), we used FasL-deficient B6.gld m ice as recipients in a Major Histocompatibility Antigen Complex-matched min or Histocompatibility Antigen-mismatched murine model for GVHD after alloge neic BMT (C3H.SW-->B6). Results. We found a significantly higher morbidity and mortality from GVHD compared to control B6 recipients. Histopathological analysis of the GVHD t arget organs demonstrated that B6.gld recipients developed significantly mo re thymic and intestinal GVHD. B6.gld recipients with GVHD demonstrated an increased expansion of donor T cells and monocytes/macrophages compared to control B6 recipients, whereas serum TNF-alpha levels were equivalent in B6 .gld recipients and control B6 recipients. Conclusion. This study demonstrates that the expression of FasL in the BMT recipient is important for the host's ability to control GVHD.