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

Marcel R.M. Van Den Brink, Ellen Moore, Kirsten J. Horndasch, James M. Crawford, George F. Murphy, Steven J. Burakoff

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Background. The Fas/Fas ligand (FasL) pathway plays an important role in a number of apoptotic processes that could be important for the development of graft-versus-host disease (GVHD) after bone marrow transplantation (BMT), such as cytolysis of target cells by cytotoxic T cells, regulation of inflammatory 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 pathophysiology of graft versus host disease (GVHD), we used FasL-deficient B6.gld mice as recipients in a Major Histocompatibility Antigen Complex-matched minor Histocompatibility Antigen-mismatched routine model for GVHD after allogeneic 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 target organs demonstrated that B6.gld recipients developed significantly more 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-α 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.

Original languageEnglish
Pages (from-to)184-191
Number of pages8
Issue number1
StatePublished - 15 Jul 2000
Externally publishedYes


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