CD4^+ヘルパーT細胞分化の基礎と臨床  [in Japanese] Transcription Factors That Regulate Helper T Cell Differentiation  [in Japanese]

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    • 臼井 崇 USUI Takashi
    • 京都大学大学院医学研究科内科学講座臨床免疫学 Department of Rheumatology and Clinical Immunology, Kyoto University, Graduate School of Medicine


  抗原特異性を持つCD4<sup>+</sup>ヘルパーT細胞(Th細胞)は,獲得免疫機構において中心的な役割を担っている.Th細胞は胸腺で教育・選択を受けた後,末梢組織に分布し,抗原提示細胞による刺激を受けると,周囲のサイトカイン環境や副刺激の種類により,IFN-γを主に産生するTh1細胞,IL-4, 5, 13を主に産生するTh2細胞,あるいはIL-17を主に産生するTh17細胞という少なくとも3種類の異なるエフェクター細胞へと分化し,それぞれ細胞性免疫,液性免疫,炎症免疫機構を担っている.Th1分化にはIL-12, STAT4, T-betシグナルが,Th2分化にはIL-4, STAT6, GATA3シグナルが,そしてTh17分化にはIL-1β, TGF-β, IL-6, IL-23, STAT3, RORγtシグナルが重要である.特に最近その概念が確立され,独立したエフェクターCD<sup>4+</sup> T細胞であるTh17細胞の解析により,これまでのTh1-Th2パラダイムだけでは説明できなかった多くの炎症病態が説明可能になってきている.今後は,このIL-17制御を目的にとした新たな薬剤開発が活発となるであろう.<br>

  Antigen-specific CD4<sup>+</sup> helper T cell (Th cell) is a major player for acquired-immunity. Th cell distribute in the peripheral tissues after educations and selections in the thymus. By stimulation from antigen presenting cell (APC), Th cell differentiate into at least three types of effector Th cells by the cytokine environments and the kinds of co-stimulatory molecules on APC. One is Th1 cell which produces IFN-γ mainly, and another is Th2 cell which produces IL-4, 5 and 13 mainly, and finally recently defined Th17 cell which produces IL-17 mainly, and these cells are charged with the a role for "cellular", "hormoral" and "inflammatory" immunity respectively. IL-12, STAT4 and T-bet signals are important for Th1 differentiation, and IL-4, STAT6 andGATA3 signals are important for Th2 differentiation, and IL-1β, TGF-β, IL-6, IL-23, STAT3, RORγt signals are important for Th17 differentiation. This newly defined Th17 cell clearly makes a big progress for understanding the pathophysiology of many inflammatory conditions. In the near future, many biologics or compounds that regulate the production or function of IL-17 will be produced aggressively.<br>


  • Jpn. J. Clin. Immunol.  

    Jpn. J. Clin. Immunol. 30(6), 419-427, 2007-12-31 

    The Japan Society for Clinical Immunology

References:  53

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