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

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    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.

    本文言語英語
    ページ(範囲)184-192
    ページ数9
    ジャーナルTransplantation
    83
    2
    DOI
    出版ステータス出版済み - 1 2007

    All Science Journal Classification (ASJC) codes

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