Effects of cyclosporin A on the activation of natural killer T cells induced by α-galactosylceramide

Takashi Kajiwara, Yukihiro Tomita, Shinji Okano, Toshiro Iwai, Youichi Yasunami, Yasunobu Yoshikai, Kikuo Nomoto, Hisataka Yasui, Ryuji Tominaga

    Research output: Contribution to journalArticle

    8 Citations (Scopus)

    Abstract

    BACKGROUND. Natural killer T (NKT) cells play crucial roles in preventing autoimmune diseases and inducing transplantation tolerance. We investigated whether cyclosporin A (CsA), which is generally used in clinical transplantation and autoimmune disease therapy, could modulate the NKT cell activation induced by α-galactosylceramide (α-GalCer) treatment. METHODS. C57BL/6 (B6) mice were given daily intraperitoneal injections of CsA (30 or 50 mg/kg) from day -1 and injected intravenously with α-GalCer (2 μg/mouse) on day 0. The kinetics of NK1.1CD3 or NK1.1Thy1.2 cells in the liver and spleen were analyzed by flow cytometry. Apoptosis of NK1.1CD3 cells, cytokine levels (interleukin [IL]-2, IL-4, IL-10 and interferon [IFN]-γ) in the recipient serum and changes in dendritic cell activation in the spleen were analyzed. RESULTS. In B6 mice treated with α-GalCer, NK1.1CD3 cells rapidly decreased in both the liver and spleen, and repopulated to their normal levels by day four, while NK1.1Thy1.2 cells rapidly decreased, expanded by day four and reduced to their normal level by day 15. When B6 mice were treated with α-GalCer plus 30 or 50 mg/kg CsA, NK1.1CD3 or NK1.1 Thy1.2cells were similarly decreased and then expanded via extensive proliferation by day seven or four, respectively. When B6 mice were treated with α-GalCer, substantial amounts of IL-2, IL-4 and IFN-γ were produced, and the surface markers of dendritic cells were upregulated. However, these cytokine productions and maturation of dendritic cells were profoundly suppressed after treatment with α-GalCer and CsA. Apoptosis of NK1.1CD3 cells was not affected in mice treated with α-GalCer or α-GalCer and CsA. CONCLUSIONS. CsA suppresses α-GalCer-induced cytokine productions and dendritic cell maturation of mouse NKT cells but does not decrease NK1.1CD3 cells on day one. The modulation of NKT-mediated immunoregulatory functions by CsA requires careful consideration in clinical transplantation and autoimmune disease therapy.

    Original languageEnglish
    Pages (from-to)184-192
    Number of pages9
    JournalTransplantation
    Volume83
    Issue number2
    DOIs
    Publication statusPublished - Jan 1 2007

    Fingerprint

    Galactosylceramides
    Natural Killer T-Cells
    Cyclosporine
    Dendritic Cells
    Autoimmune Diseases
    Spleen
    Cytokines
    Interleukin-4
    Interferons
    Interleukin-2
    Transplantation
    Apoptosis
    Transplantation Tolerance
    Liver
    Therapeutics
    Intraperitoneal Injections
    Interleukin-10
    Flow Cytometry
    Serum

    All Science Journal Classification (ASJC) codes

    • Transplantation

    Cite this

    Kajiwara, T., Tomita, Y., Okano, S., Iwai, T., Yasunami, Y., Yoshikai, Y., ... Tominaga, R. (2007). Effects of cyclosporin A on the activation of natural killer T cells induced by α-galactosylceramide. Transplantation, 83(2), 184-192. https://doi.org/10.1097/01.tp.0000250573.50046.89

    Effects of cyclosporin A on the activation of natural killer T cells induced by α-galactosylceramide. / Kajiwara, Takashi; Tomita, Yukihiro; Okano, Shinji; Iwai, Toshiro; Yasunami, Youichi; Yoshikai, Yasunobu; Nomoto, Kikuo; Yasui, Hisataka; Tominaga, Ryuji.

    In: Transplantation, Vol. 83, No. 2, 01.01.2007, p. 184-192.

    Research output: Contribution to journalArticle

    Kajiwara, T, Tomita, Y, Okano, S, Iwai, T, Yasunami, Y, Yoshikai, Y, Nomoto, K, Yasui, H & Tominaga, R 2007, 'Effects of cyclosporin A on the activation of natural killer T cells induced by α-galactosylceramide', Transplantation, vol. 83, no. 2, pp. 184-192. https://doi.org/10.1097/01.tp.0000250573.50046.89
    Kajiwara, Takashi ; Tomita, Yukihiro ; Okano, Shinji ; Iwai, Toshiro ; Yasunami, Youichi ; Yoshikai, Yasunobu ; Nomoto, Kikuo ; Yasui, Hisataka ; Tominaga, Ryuji. / Effects of cyclosporin A on the activation of natural killer T cells induced by α-galactosylceramide. In: Transplantation. 2007 ; Vol. 83, No. 2. pp. 184-192.
    @article{5b838e4e4959454f97a47d8ad58f933f,
    title = "Effects of cyclosporin A on the activation of natural killer T cells induced by α-galactosylceramide",
    abstract = "BACKGROUND. Natural killer T (NKT) cells play crucial roles in preventing autoimmune diseases and inducing transplantation tolerance. We investigated whether cyclosporin A (CsA), which is generally used in clinical transplantation and autoimmune disease therapy, could modulate the NKT cell activation induced by α-galactosylceramide (α-GalCer) treatment. METHODS. C57BL/6 (B6) mice were given daily intraperitoneal injections of CsA (30 or 50 mg/kg) from day -1 and injected intravenously with α-GalCer (2 μg/mouse) on day 0. The kinetics of NK1.1CD3 or NK1.1Thy1.2 cells in the liver and spleen were analyzed by flow cytometry. Apoptosis of NK1.1CD3 cells, cytokine levels (interleukin [IL]-2, IL-4, IL-10 and interferon [IFN]-γ) in the recipient serum and changes in dendritic cell activation in the spleen were analyzed. RESULTS. In B6 mice treated with α-GalCer, NK1.1CD3 cells rapidly decreased in both the liver and spleen, and repopulated to their normal levels by day four, while NK1.1Thy1.2 cells rapidly decreased, expanded by day four and reduced to their normal level by day 15. When B6 mice were treated with α-GalCer plus 30 or 50 mg/kg CsA, NK1.1CD3 or NK1.1 Thy1.2cells were similarly decreased and then expanded via extensive proliferation by day seven or four, respectively. When B6 mice were treated with α-GalCer, substantial amounts of IL-2, IL-4 and IFN-γ were produced, and the surface markers of dendritic cells were upregulated. However, these cytokine productions and maturation of dendritic cells were profoundly suppressed after treatment with α-GalCer and CsA. Apoptosis of NK1.1CD3 cells was not affected in mice treated with α-GalCer or α-GalCer and CsA. CONCLUSIONS. CsA suppresses α-GalCer-induced cytokine productions and dendritic cell maturation of mouse NKT cells but does not decrease NK1.1CD3 cells on day one. The modulation of NKT-mediated immunoregulatory functions by CsA requires careful consideration in clinical transplantation and autoimmune disease therapy.",
    author = "Takashi Kajiwara and Yukihiro Tomita and Shinji Okano and Toshiro Iwai and Youichi Yasunami and Yasunobu Yoshikai and Kikuo Nomoto and Hisataka Yasui and Ryuji Tominaga",
    year = "2007",
    month = "1",
    day = "1",
    doi = "10.1097/01.tp.0000250573.50046.89",
    language = "English",
    volume = "83",
    pages = "184--192",
    journal = "Transplantation",
    issn = "0041-1337",
    publisher = "Lippincott Williams and Wilkins",
    number = "2",

    }

    TY - JOUR

    T1 - Effects of cyclosporin A on the activation of natural killer T cells induced by α-galactosylceramide

    AU - Kajiwara, Takashi

    AU - Tomita, Yukihiro

    AU - Okano, Shinji

    AU - Iwai, Toshiro

    AU - Yasunami, Youichi

    AU - Yoshikai, Yasunobu

    AU - Nomoto, Kikuo

    AU - Yasui, Hisataka

    AU - Tominaga, Ryuji

    PY - 2007/1/1

    Y1 - 2007/1/1

    N2 - BACKGROUND. Natural killer T (NKT) cells play crucial roles in preventing autoimmune diseases and inducing transplantation tolerance. We investigated whether cyclosporin A (CsA), which is generally used in clinical transplantation and autoimmune disease therapy, could modulate the NKT cell activation induced by α-galactosylceramide (α-GalCer) treatment. METHODS. C57BL/6 (B6) mice were given daily intraperitoneal injections of CsA (30 or 50 mg/kg) from day -1 and injected intravenously with α-GalCer (2 μg/mouse) on day 0. The kinetics of NK1.1CD3 or NK1.1Thy1.2 cells in the liver and spleen were analyzed by flow cytometry. Apoptosis of NK1.1CD3 cells, cytokine levels (interleukin [IL]-2, IL-4, IL-10 and interferon [IFN]-γ) in the recipient serum and changes in dendritic cell activation in the spleen were analyzed. RESULTS. In B6 mice treated with α-GalCer, NK1.1CD3 cells rapidly decreased in both the liver and spleen, and repopulated to their normal levels by day four, while NK1.1Thy1.2 cells rapidly decreased, expanded by day four and reduced to their normal level by day 15. When B6 mice were treated with α-GalCer plus 30 or 50 mg/kg CsA, NK1.1CD3 or NK1.1 Thy1.2cells were similarly decreased and then expanded via extensive proliferation by day seven or four, respectively. When B6 mice were treated with α-GalCer, substantial amounts of IL-2, IL-4 and IFN-γ were produced, and the surface markers of dendritic cells were upregulated. However, these cytokine productions and maturation of dendritic cells were profoundly suppressed after treatment with α-GalCer and CsA. Apoptosis of NK1.1CD3 cells was not affected in mice treated with α-GalCer or α-GalCer and CsA. CONCLUSIONS. CsA suppresses α-GalCer-induced cytokine productions and dendritic cell maturation of mouse NKT cells but does not decrease NK1.1CD3 cells on day one. The modulation of NKT-mediated immunoregulatory functions by CsA requires careful consideration in clinical transplantation and autoimmune disease therapy.

    AB - BACKGROUND. Natural killer T (NKT) cells play crucial roles in preventing autoimmune diseases and inducing transplantation tolerance. We investigated whether cyclosporin A (CsA), which is generally used in clinical transplantation and autoimmune disease therapy, could modulate the NKT cell activation induced by α-galactosylceramide (α-GalCer) treatment. METHODS. C57BL/6 (B6) mice were given daily intraperitoneal injections of CsA (30 or 50 mg/kg) from day -1 and injected intravenously with α-GalCer (2 μg/mouse) on day 0. The kinetics of NK1.1CD3 or NK1.1Thy1.2 cells in the liver and spleen were analyzed by flow cytometry. Apoptosis of NK1.1CD3 cells, cytokine levels (interleukin [IL]-2, IL-4, IL-10 and interferon [IFN]-γ) in the recipient serum and changes in dendritic cell activation in the spleen were analyzed. RESULTS. In B6 mice treated with α-GalCer, NK1.1CD3 cells rapidly decreased in both the liver and spleen, and repopulated to their normal levels by day four, while NK1.1Thy1.2 cells rapidly decreased, expanded by day four and reduced to their normal level by day 15. When B6 mice were treated with α-GalCer plus 30 or 50 mg/kg CsA, NK1.1CD3 or NK1.1 Thy1.2cells were similarly decreased and then expanded via extensive proliferation by day seven or four, respectively. When B6 mice were treated with α-GalCer, substantial amounts of IL-2, IL-4 and IFN-γ were produced, and the surface markers of dendritic cells were upregulated. However, these cytokine productions and maturation of dendritic cells were profoundly suppressed after treatment with α-GalCer and CsA. Apoptosis of NK1.1CD3 cells was not affected in mice treated with α-GalCer or α-GalCer and CsA. CONCLUSIONS. CsA suppresses α-GalCer-induced cytokine productions and dendritic cell maturation of mouse NKT cells but does not decrease NK1.1CD3 cells on day one. The modulation of NKT-mediated immunoregulatory functions by CsA requires careful consideration in clinical transplantation and autoimmune disease therapy.

    UR - http://www.scopus.com/inward/record.url?scp=33846618657&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=33846618657&partnerID=8YFLogxK

    U2 - 10.1097/01.tp.0000250573.50046.89

    DO - 10.1097/01.tp.0000250573.50046.89

    M3 - Article

    C2 - 17264815

    AN - SCOPUS:33846618657

    VL - 83

    SP - 184

    EP - 192

    JO - Transplantation

    JF - Transplantation

    SN - 0041-1337

    IS - 2

    ER -