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 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 murine 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. B6gld 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.


CONCLUSIONS
This study demonstrates that the expression of FasL in the BMT recipient is important for the host's ability to control GVHD.
Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA.
M R
MR
van den Brink
E
E
Moore
K J
KJ
Horndasch
J M
JM
Crawford
G F
GF
Murphy
S J
SJ
Burakoff
D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D004198:Disease Susceptibility; D053222:Fas Ligand Protein; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology*; D008264:Macrophages / Q000502:physiology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha