Mechanisms of cyclophosphamide-induced tolerance to ie-encoded alloantigens—evidence of clonal deletion in mhc antigen-reactive cells for skin allograft rejection

Yukihiro Tomita, Katsuhiko Ayukawa, Yasunobu Yoshikai, Klkuo Nomoto

    Research output: Contribution to journalArticle

    16 Citations (Scopus)

    Abstract

    Transplantation tolerance across H-2D plus IE antigen barriers has been achieved when BlO.Thyl.l (Kb, IAb, IE", Db; Thyl.l) mice were primed i.v. with 9×l07 spleen cells plus 3×l07 bone marrow cells from B10.A(5R) (Kb, IAb, IE, Db; Thyl.2) and treated i.p. with 200 mg/kg of cyclophosphamide (CP) two days later. The tolerant state was confirmed by prolonged acceptance of donor-type skin grafts, and in vitro unresponsiveness to donor antigens. From the early stage of tolerant state, Vβ11+ or Vβ5+ T cells expressing CD4 or CD8 accessory molecules were markedly decreased in the periphery of the tolerant mice. Moreover, neither CD4+CD8 nor CD4CD8+ thymocytes bearing a high density of Vβ11 or Vβ5 were detected in the chimeric thymus. The intrathymic clonal deletion appeared to bemaintained in some of the recipient mice even after the disappearance of detectable mixed chimerism in the late stage. These results suggest that the mechanisms of the CP-induced tolerance include the destruction of the IE (and probably H-2D) reactive T cells in the periphery followed by the intrathymic clonal deletion of T cells reactive against these antigens. These results directly show the strong correlation between transplantation tolerance to H-2 alloantigens and the disappearance of alloreactive T cells in both the periphery and thymus.

    Original languageEnglish
    Pages (from-to)602-612
    Number of pages11
    JournalTransplantation
    Volume53
    Issue number3
    DOIs
    Publication statusPublished - Jan 1 1992

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    Clonal Deletion
    Cyclophosphamide
    Allografts
    Transplantation Tolerance
    T-Lymphocytes
    Antigens
    Skin
    Thymus Gland
    Chimerism
    Isoantigens
    Thymocytes
    Bone Marrow Cells
    Spleen
    Transplants

    All Science Journal Classification (ASJC) codes

    • Transplantation

    Cite this

    Mechanisms of cyclophosphamide-induced tolerance to ie-encoded alloantigens—evidence of clonal deletion in mhc antigen-reactive cells for skin allograft rejection. / Tomita, Yukihiro; Ayukawa, Katsuhiko; Yoshikai, Yasunobu; Nomoto, Klkuo.

    In: Transplantation, Vol. 53, No. 3, 01.01.1992, p. 602-612.

    Research output: Contribution to journalArticle

    Tomita, Yukihiro ; Ayukawa, Katsuhiko ; Yoshikai, Yasunobu ; Nomoto, Klkuo. / Mechanisms of cyclophosphamide-induced tolerance to ie-encoded alloantigens—evidence of clonal deletion in mhc antigen-reactive cells for skin allograft rejection. In: Transplantation. 1992 ; Vol. 53, No. 3. pp. 602-612.
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    abstract = "Transplantation tolerance across H-2D plus IE antigen barriers has been achieved when BlO.Thyl.l (Kb, IAb, IE{"}, Db; Thyl.l) mice were primed i.v. with 9×l07 spleen cells plus 3×l07 bone marrow cells from B10.A(5R) (Kb, IAb, IE−, Db; Thyl.2) and treated i.p. with 200 mg/kg of cyclophosphamide (CP) two days later. The tolerant state was confirmed by prolonged acceptance of donor-type skin grafts, and in vitro unresponsiveness to donor antigens. From the early stage of tolerant state, Vβ11+ or Vβ5+ T cells expressing CD4 or CD8 accessory molecules were markedly decreased in the periphery of the tolerant mice. Moreover, neither CD4+CD8− nor CD4−CD8+ thymocytes bearing a high density of Vβ11 or Vβ5 were detected in the chimeric thymus. The intrathymic clonal deletion appeared to bemaintained in some of the recipient mice even after the disappearance of detectable mixed chimerism in the late stage. These results suggest that the mechanisms of the CP-induced tolerance include the destruction of the IE (and probably H-2D) reactive T cells in the periphery followed by the intrathymic clonal deletion of T cells reactive against these antigens. These results directly show the strong correlation between transplantation tolerance to H-2 alloantigens and the disappearance of alloreactive T cells in both the periphery and thymus.",
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