Indefinite allograft survival mediated by donor bone marrow is dependent on the presence of a functional CD95 (Fas) gene in recipients.
It is well documented that donor bone marrow in combination with peri-transplant anti-thymocyte globulin (ATG) administration induces transplantation tolerance in a variety of animal models. Our previous work showed that the ability of donor marrow to induce tolerance was dependent on the presence of CD95 ligand (Fas-ligand) on the donor cells. In this study we investigate whether CD95 (Fas) on the recipient cells is required. By comparing skin allograft survival times between wild-type C57BL/6 ATG-treated recipients and C57BL/6(lpr/lpr) ATG-treated recipients (which do not have a functional CD95 gene), we show that donor bone marrow could induce indefinite transplant survival (median survival time >200 days) only in recipients with a functional CD95 gene. Thus, we conclude that the CD95 ligand-CD95 apoptotic pathway plays a major role in donor bone marrow-induced transplantation tolerance.
Goldstein
D R
DR
Division of Cardiovascular Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294-007, USA.
Thomas
J M
JM
Kirklin
J K
JK
George
J F
JF
D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000379:methods*; D006085:Graft Survival / Q000235:genetics*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D019520:Living Donors; D051379:Mice; D008810:Mice, Inbred C57BL; D014184:Transplantation, Homologous; D019014:fas Receptor / Q000235:genetics*
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D019014:fas Receptor