樹状細胞を介する invariant natural killer T 細胞の寛容誘導 Induction of invariant NKT cell anergy by dendritic cells

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著者

    • 伊豫田 智典 IYODA Tomonori
    • 京都大学 大学院生命科学研究科 高次生命科学専攻 生体応答学分野 Laboratory of Immunobiology, Department of Animal Development and Physiology, Division of Systemic Life Science, Graduate School of Biostudies, Kyoto University
    • 牛田 万貴 USHIDA Maki
    • 京都大学 大学院生命科学研究科 高次生命科学専攻 生体応答学分野 Laboratory of Immunobiology, Department of Animal Development and Physiology, Division of Systemic Life Science, Graduate School of Biostudies, Kyoto University
    • 稲葉 カヨ INABA Kayo
    • 京都大学 大学院生命科学研究科 高次生命科学専攻 生体応答学分野 Laboratory of Immunobiology, Department of Animal Development and Physiology, Division of Systemic Life Science, Graduate School of Biostudies, Kyoto University

抄録

<p>Invariant natural killer T cells (iNKT cells) are a subset of αβ T cell receptor (TCR) positive T cells and express Vα 14 (mouse) or Vα24 TCR (human). iNKT cells recognize lipid antigen, such as α-galactosylceramide (αGC) loaded on CD1d, which is non-classical major histocompatibility complex (MHC) class I-like molecule, and rapidly produce a huge amount of cytokines after stimulation. Although CD1d molecules were expressed on various cell types, dendritic cells (DCs) most efficiently presented αGC to iNKT cells both <i>in vitro</i> and <i>in vivo</i>. Through the antigen-presentation, DCs and iNKT cells reciprocally activated each other. Interestingly, although iNKT cells received both TCR and co-stimulatory stimuli from DCs, they became unresponsive to secondary stimulation (anergy). When restimulated in the prensene of exogenous IL-2, anergized iNKT cells produced IL-4 comparable to control cells but not IFN-γ. After primary stimulation, programmed death-1 (PD-1) molecules were expressed at high level on iNKT cells for certain period. However, αGCactivated iNKT cells in PD-1 deficient mice became anergic as in normal mice. Furthermore, anti-PD-1 blocking mAb was unable to restore their responsiveness. When iNKT cells were stimulated with immobilized anti-CD3 mAb in the presence or absence of anti-CD28 mAb, they produced cytokines in a dose-dependent manner. Unlike in conventional naïve CD4 T cells, the strong TCR-mediated signaling with co-stimulation rendered iNKT cells anergic to the subsequent stimulation with αGC and spleen DCs. Consistent with <i>in vitro</i> assay, the injection of αGC-pulsed DCs was more potent in inducing anergy than B cells. These results indicate that strong TCR-mediated activation with co-stimulation provides signals induces the anergic state in iNKT cells.</p>

収録刊行物

  • Cytometry research : 日本サイトメトリー学会機関誌

    Cytometry research : 日本サイトメトリー学会機関誌 22(1), 25-30, 2012-03-25

    日本サイトメトリー学会

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