Regulatory roles of NKT cells in the induction and maintenance of cyclophosphamide-induced tolerance

Toshiro Iwai, Yukihiro Tomita, Shinji Okano, Ichiro Shimizu, Yohichi Yasunami, Takashi Kajiwara, Yasunobu Yoshikai, Masaru Taniguchi, Kikuo Nomoto, Hisataka Yasui

    Research output: Contribution to journalArticle

    21 Citations (Scopus)

    Abstract

    We have previously reported the sequential mechanisms of cyclophosphamide (CP)-induced tolerance. Permanent acceptance of donor skin graft is readily induced in the MHC-matched and minor Ag-mismatched recipients after treatment with donor spleen cells and CP. In the present study, we have elucidated the roles of NKT cells in CP-induced skin allograft tolerance. BALB/c AnNCrj (H-2d, Lyt-1.2, and Mls-1b) wild-type (WT) mice or Vα14 NKT knockout (KO) (BALB/c) mice were used as recipients, and DBA/2 NCrj (H-2d, Lyt-1.1, and Mls-1a) mice were used as donors. Recipient mice were primed with 1 × 108 donor SC i.v. on day 0, followed by 200 mg/kg CP i.p. on day 2. Donor mixed chimerism and permanent acceptance of donor skin allografts were observed in the WT recipients. However, donor skin allgrafts were rejected in NKT KO recipient mice. In addition, the donor reactive Vβ6+ T cells were observed in the thymus of a NKT KO recipient Reconstruction of NKT cells from WT mice restored the acceptance of donor skin allografts. In addition, donor grafts were partially accepted in the thymectomized NKT KO recipient mice. Furthermore, the tolerogen-specific suppressor cell was observed in thymectomized NKT KO recipient mice, suggesting the generation of regulatory T cells in the absence of NTK cells. Our results suggest that NKT cells are essential for CP-induced tolerance and may have a role in the establishment of mixed chimerism, resulting in clonal deletion of donor-reactive T cells in the recipient thymus.

    Original languageEnglish
    Pages (from-to)8400-8409
    Number of pages10
    JournalJournal of Immunology
    Volume177
    Issue number12
    DOIs
    Publication statusPublished - Dec 15 2006

    Fingerprint

    Natural Killer T-Cells
    Cyclophosphamide
    Maintenance
    Skin
    Knockout Mice
    Chimerism
    Thymus Gland
    Allografts
    Clonal Deletion
    Transplantation Tolerance
    T-Lymphocytes
    Transplants
    Regulatory T-Lymphocytes
    Spleen

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

    Cite this

    Iwai, T., Tomita, Y., Okano, S., Shimizu, I., Yasunami, Y., Kajiwara, T., ... Yasui, H. (2006). Regulatory roles of NKT cells in the induction and maintenance of cyclophosphamide-induced tolerance. Journal of Immunology, 177(12), 8400-8409. https://doi.org/10.4049/jimmunol.177.12.8400

    Regulatory roles of NKT cells in the induction and maintenance of cyclophosphamide-induced tolerance. / Iwai, Toshiro; Tomita, Yukihiro; Okano, Shinji; Shimizu, Ichiro; Yasunami, Yohichi; Kajiwara, Takashi; Yoshikai, Yasunobu; Taniguchi, Masaru; Nomoto, Kikuo; Yasui, Hisataka.

    In: Journal of Immunology, Vol. 177, No. 12, 15.12.2006, p. 8400-8409.

    Research output: Contribution to journalArticle

    Iwai, T, Tomita, Y, Okano, S, Shimizu, I, Yasunami, Y, Kajiwara, T, Yoshikai, Y, Taniguchi, M, Nomoto, K & Yasui, H 2006, 'Regulatory roles of NKT cells in the induction and maintenance of cyclophosphamide-induced tolerance', Journal of Immunology, vol. 177, no. 12, pp. 8400-8409. https://doi.org/10.4049/jimmunol.177.12.8400
    Iwai, Toshiro ; Tomita, Yukihiro ; Okano, Shinji ; Shimizu, Ichiro ; Yasunami, Yohichi ; Kajiwara, Takashi ; Yoshikai, Yasunobu ; Taniguchi, Masaru ; Nomoto, Kikuo ; Yasui, Hisataka. / Regulatory roles of NKT cells in the induction and maintenance of cyclophosphamide-induced tolerance. In: Journal of Immunology. 2006 ; Vol. 177, No. 12. pp. 8400-8409.
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    abstract = "We have previously reported the sequential mechanisms of cyclophosphamide (CP)-induced tolerance. Permanent acceptance of donor skin graft is readily induced in the MHC-matched and minor Ag-mismatched recipients after treatment with donor spleen cells and CP. In the present study, we have elucidated the roles of NKT cells in CP-induced skin allograft tolerance. BALB/c AnNCrj (H-2d, Lyt-1.2, and Mls-1b) wild-type (WT) mice or Vα14 NKT knockout (KO) (BALB/c) mice were used as recipients, and DBA/2 NCrj (H-2d, Lyt-1.1, and Mls-1a) mice were used as donors. Recipient mice were primed with 1 × 108 donor SC i.v. on day 0, followed by 200 mg/kg CP i.p. on day 2. Donor mixed chimerism and permanent acceptance of donor skin allografts were observed in the WT recipients. However, donor skin allgrafts were rejected in NKT KO recipient mice. In addition, the donor reactive Vβ6+ T cells were observed in the thymus of a NKT KO recipient Reconstruction of NKT cells from WT mice restored the acceptance of donor skin allografts. In addition, donor grafts were partially accepted in the thymectomized NKT KO recipient mice. Furthermore, the tolerogen-specific suppressor cell was observed in thymectomized NKT KO recipient mice, suggesting the generation of regulatory T cells in the absence of NTK cells. Our results suggest that NKT cells are essential for CP-induced tolerance and may have a role in the establishment of mixed chimerism, resulting in clonal deletion of donor-reactive T cells in the recipient thymus.",
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