title: Enhanced allograft survival induced by posttransplant donor spleen cell infusion occurs via a mechanism that is distinct from the mechanism of enhancement by donor bone marrow.
abstract: BACKGROUND
  Our previous studies have shown that the ability of donor bone marrow to augment skin graft survival in antithymocyte serum (ATS)-treated recipients is dependent on the presence of functional CD95-ligand (Fas-ligand) molecules on donor cells. Because donor spleen cells can augment graft survival to a similar degree in the same model, we investigated whether the donor spleen cell effect was also dependent on the presence of CD95-ligand on donor cells and CD95 on recipient cells.
  
  
  METHODS
  Mutant mice bearing defects in the expression of CD95 (lpr mutation) and CD95-ligand (gld mutation) were used as recipients and cell donors, respectively. Recipients were injected with rabbit ATS on days -1 and +2, and then were injected with 5x10(7) spleen cells on day +7. Skin graft survival was compared and correlated with the use of mutant mice as recipients and cell donors.
  
  
  RESULTS
  The combination of ATS and infusions of wild-type [median survival (MST)=44 days, P=0.0004] and gld (mutant CD95-ligand, MST=37 days, P=0.02) donor spleen cells enhanced C3H graft survival, compared with (C57BL/6 x A)F1 recipients treated with ATS alone (MST=27 days). Furthermore, C57BL/6 lpr (CD95-deficient) strain recipients treated with ATS and donor spleen cells demonstrated enhanced B10.D2(R107) strain skin graft survival (MST=44 days, P=0.003), compared with C57BL/6 lpr recipients treated with ATS alone (MST=31 days). Wild-type C57BL/6 recipients treated in the same manner also exhibited an extension of graft survival (MST=64 days) versus controls treated with ATS alone (MST=31 days).
  
  
  CONCLUSIONS
  The data demonstrate that the ability of donor spleen cells to augment allograft survival is not dependent on the CD95/CD95-ligand pathway; therefore the deletion of allospecific cells by donor spleen cells may be induced via a pathway other than deletion by donor bone marrow cells.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, 35294-0007, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Goldstein
authors.forename: T
authors.initials: T
authors.lastname: Chang
authors.forename: S D
authors.initials: SD
authors.lastname: Sweeney
authors.forename: J K
authors.initials: JK
authors.lastname: Kirklin
authors.forename: J M
authors.initials: JM
authors.lastname: Thomas
authors.forename: J F
authors.initials: JF
authors.lastname: George
mesh_terms: D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D017690:Cell Transplantation; D006085:Graft Survival; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D011817:Rabbits; D013154:Spleen / Q000166:cytology*; D014184:Transplantation, Homologous
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents