The critical role of Fas-Fas ligand interaction in donor-specific transfusion-induced tolerance to H-Y antigen

Ryosuke Minagawa, Shinji Okano, Yukihiro Tomita, Kenji Kishihara, Hisakata Yamada, Kenichi Nomoto, Mitsuo Shimada, Yoshihiko Maehara, Keizo Sugimachi, Yasunobu Yoshikai, Kikuo Nomoto

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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-Faslpr (lpr) female mice were intravenously injected with B6, lpr, or B6-FasLgld (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.

Original languageEnglish
Pages (from-to)799-806
Number of pages8
JournalTransplantation
Volume78
Issue number6
DOIs
Publication statusPublished - Sep 27 2004

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H-Y Antigen
Fas Ligand Protein
Skin
Spleen
B-Lymphocytes
Mixed Lymphocyte Culture Test
Clonal Deletion
Tissue Survival
Graft Rejection

All Science Journal Classification (ASJC) codes

  • Transplantation

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The critical role of Fas-Fas ligand interaction in donor-specific transfusion-induced tolerance to H-Y antigen. / Minagawa, Ryosuke; Okano, Shinji; Tomita, Yukihiro; Kishihara, Kenji; Yamada, Hisakata; Nomoto, Kenichi; Shimada, Mitsuo; Maehara, Yoshihiko; Sugimachi, Keizo; Yoshikai, Yasunobu; Nomoto, Kikuo.

In: Transplantation, Vol. 78, No. 6, 27.09.2004, p. 799-806.

Research output: Contribution to journalArticle

Minagawa, R, Okano, S, Tomita, Y, Kishihara, K, Yamada, H, Nomoto, K, Shimada, M, Maehara, Y, Sugimachi, K, Yoshikai, Y & Nomoto, K 2004, 'The critical role of Fas-Fas ligand interaction in donor-specific transfusion-induced tolerance to H-Y antigen', Transplantation, vol. 78, no. 6, pp. 799-806. https://doi.org/10.1097/01.TP.0000129799.96439.6F
Minagawa, Ryosuke ; Okano, Shinji ; Tomita, Yukihiro ; Kishihara, Kenji ; Yamada, Hisakata ; Nomoto, Kenichi ; Shimada, Mitsuo ; Maehara, Yoshihiko ; Sugimachi, Keizo ; Yoshikai, Yasunobu ; Nomoto, Kikuo. / The critical role of Fas-Fas ligand interaction in donor-specific transfusion-induced tolerance to H-Y antigen. In: Transplantation. 2004 ; Vol. 78, No. 6. pp. 799-806.
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AU - Minagawa, Ryosuke

AU - Okano, Shinji

AU - Tomita, Yukihiro

AU - Kishihara, Kenji

AU - Yamada, Hisakata

AU - Nomoto, Kenichi

AU - Shimada, Mitsuo

AU - Maehara, Yoshihiko

AU - Sugimachi, Keizo

AU - Yoshikai, Yasunobu

AU - Nomoto, Kikuo

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N2 - 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-Faslpr (lpr) female mice were intravenously injected with B6, lpr, or B6-FasLgld (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.

AB - 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-Faslpr (lpr) female mice were intravenously injected with B6, lpr, or B6-FasLgld (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.

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