Dissection of effector pathways in the host-versus-graft response to bone marrow transplantation.
We have dissected the role of the primary cytotoxic pathways Fas-FasL and perforin-granzyme in host-versus-graft reactions after allogeneic bone marrow transplantation. Sublethally irradiated female recipient mice deficient for FasL (B6.gld) or perforin (B6.prf-/-) were transplanted with bone marrow from B6 male donors. Donor engraftment in B6.prf-/- recipients was higher when compared with B6.gld, particularly when assessed by in vivo killing, demonstrating the importance of the perforin pathway over the Fas-FasL pathway. In the absence of both pathways, however, donor bone marrow engraftment was not fully restored identifying a role for an additional pathway(s) in the host-versus-graft response.
Weng
Ling
L
Department of Haematology, Division of Investigative Sciences, Imperial College, Hammersmith Hospital, London, United Kingdom.
Addey
Caroline
C
Warrens
Anthony N
AN
Dyson
Julian
J
Chai
Jian-Guo
JG
Dazzi
Francesco
F
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000502:physiology*; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000528:radiation effects; D006182:H-Y Antigen / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation; D006789:Host vs Graft Reaction / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D054353:Perforin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000637:transplantation; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
D053222:Fas Ligand Protein; D006182:H-Y Antigen; D019014:fas Receptor; D054353:Perforin