The critical role of Fas-Fas ligand interaction in donor-specific transfusion-induced tolerance to H-Y antigen.
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.
Minagawa
Ryosuke
R
Department of Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Okano
Shinji
S
Tomita
Yukihiro
Y
Kishihara
Kenji
K
Yamada
Hisakata
H
Nomoto
Kenichi
K
Shimada
Mitsuo
M
Maehara
Yoshihiko
Y
Sugimachi
Keizo
K
Yoshikai
Yasunobu
Y
Nomoto
Kikuo
K
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*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D006182:H-Y Antigen; D008562:Membrane Glycoproteins; D019014:fas Receptor