Shibuya Akira
Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan.
Int J Hematol. 2003 Jul;78(1):1-6. doi: 10.1007/BF02983233.
Over the last decade, progress in molecular and cellular biology and gene targeting techniques has removed veils from the mysteries of natural killer (NK) cell development and function. NK cells are derived from hematopoietic stem cells, for which stem cell factor or Flt3 ligand is required in the early stage of differentiation to NK cell progenitors. Interleukin 15 then plays a crucial role for differentiation and/or maturation of NK progenitors into functional NK cells. Several members of the zinc finger, ETS, and interferon regulatory factor transcription factor families are also involved in the lineage commitment of hematopoietic stem or progenitors into NK cells. Animal models as well as patients deficient in NK cells have provided formal evidence that NK cells play an important role in vivo for innate immunity against tumors and viral infections and for linkage to adaptive immunity. Moreover, recent studies have revealed novel human NK cell subsets in peripheral blood that have the phenotypical characteristics CD3- CD16+ CD56+ and CD3- CD16- CD56bright, which are mainly involved in cytotoxicity and cytokine-mediated immunoregulation, respectively.
在过去十年中，分子与细胞生物学以及基因靶向技术的进展揭开了自然杀伤（NK）细胞发育和功能之谜的面纱。NK细胞源自造血干细胞，在分化为NK细胞祖细胞的早期阶段，干细胞因子或Flt3配体是必需的。然后，白细胞介素15在NK祖细胞分化和/或成熟为功能性NK细胞的过程中发挥关键作用。锌指、ETS和干扰素调节因子转录因子家族的几个成员也参与造血干细胞或祖细胞向NK细胞的谱系定向分化。动物模型以及NK细胞缺陷的患者提供了确凿证据，表明NK细胞在体内对肿瘤和病毒感染的固有免疫以及与适应性免疫的联系中发挥重要作用。此外，最近的研究揭示了外周血中具有CD3-CD16+CD56+和CD3-CD16-CD56bright表型特征的新型人类NK细胞亚群，它们分别主要参与细胞毒性和细胞因子介导的免疫调节。
