title: The critical role of Fas-Fas ligand interaction in donor-specific transfusion-induced tolerance to H-Y antigen.
abstract: BACKGROUND
  Donor-specific transfusion (DST) has been clinically used to enhance the survival of transplanted organs, and it has been shown in mice to induce tolerance to male (H-Y) antigen (Ag). Although the biologic mechanisms that initiate and maintain DST-induced tolerance involve clonal deletion, induction of anergy, and generation of regulatory cells, the molecules essential to tolerance induction are still unclear. In this study, we investigated the role of Fas-FasL interaction in DST-induced tolerance to H-Y Ag.
  
  
  METHODS
  C57BL/6 (B6) or B6-Fas(lpr) (lpr) female mice were intravenously injected with B6, lpr, or B6-FasL(gld) (gld) male spleen cells (SC). B6 male skin grafts, mixed lymphocyte reaction (MLR) assay, and cytotoxicity assay (CTL) were performed 7 days after DST. In some experiments, purified B-cells were used as transfused cells.
  
  
  RESULTS
  B6 female mice treated with B6 male SC permanently accepted B6 male skins, whereas untreated B6 or lpr female mice rejected B6 male skins. On the other hand, B6 female mice treated with gld male SC acceleratingly rejected male skin, as did lpr female mice treated with B6 or gld male SC. The recipient mice in the experimental groups, in which DST resulted in the accelerated rejection of the skin grafts, had strong allo-responses to H-Y Ag in MLR and CTL. Further, B6 female mice treated with gld male B-cells acceleratingly rejected male skins, whereas B6 female mice treated with B6 or lpr male B-cells from mice accepted male skins.
  
  
  CONCLUSIONS
  These findings suggest that the interaction between FasL upon infused SC, especially upon B-cells and Fas in a recipient, is essential in DST-induced tolerance to H-Y Ag.
authors.affiliation: Department of Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Minagawa
authors.forename: Shinji
authors.initials: S
authors.lastname: Okano
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Tomita
authors.forename: Kenji
authors.initials: K
authors.lastname: Kishihara
authors.forename: Hisakata
authors.initials: H
authors.lastname: Yamada
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nomoto
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Shimada
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
authors.forename: Keizo
authors.initials: K
authors.lastname: Sugimachi
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Yoshikai
authors.forename: Kikuo
authors.initials: K
authors.lastname: Nomoto
mesh_terms: D000818:Animals; D017690:Cell Transplantation; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein; D005260:Female; D006182:H-Y Antigen / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016038:Skin Transplantation / Q000276:immunology*; D018183:Transplantation Chimera; D023001:Transplantation Tolerance / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology*
chemical_list: D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D006182:H-Y Antigen; D008562:Membrane Glycoproteins; D019014:fas Receptor