NK cell phenotypic and functional heterogeneities and molecular mechanisms of cytotoxicity.

NK cell phenotypic and functional heterogeneities and molecular mechanisms of cytotoxicity.
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NK 细胞表型和功能异质性以及细胞毒性的分子机制。

DOI:
10.1615/critrevoncog.2014010804
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发表时间:
2014
影响因子:
--
通讯作者:
B. Bonavida
B. Bonavida
中科院分区:
--
文献类型:
--
作者:
B. Bonavida

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自然杀伤 (NK) 细胞是四十年前由 Kiessling 和 Herberman 团队独立发现的。从那时起,NK 细胞的功能和分子特性及其临床相关性方面取得了重大进展。 NK细胞的重要特征是它们无法杀死正常细胞,但对感染或转化的细胞具有高度细胞毒性。随着 NK 细胞上激活和抑制受体以及靶细胞上相应配体的发现,这种歧视已在很大程度上得到解决。本文简要综述了与 NK 细胞相关的几个问题:(1) NK 细胞的表型特性,(2) NK 细胞活性的异质性,(3) 三大 NK 亚群(Free、Binder 和 Killer)的测定,(4) NK 亚群的成熟和激活,(5) NK 细胞对各种细胞因子的反应,(6) 靶点诱导的 NK 细胞失活和细胞死亡,(7) NK 细胞的多种机制。细胞介导的细胞毒性,(8) NK 细胞毒性因子 (NKCF) 的表征,以及 (9) 膜流动性在细胞毒性中的作用。在罗恩·赫伯曼 (Ron Herberman) 的领导下,NK 细胞被发现后不久,这些主题就按时间顺序开始描述,我对他深表感激。
Natural killer (NK) cells were discovered four decades ago, independently, by the Kiessling and Herberman groups. Since then, significant advances have accrued regarding the functional and molecular properties of NK cells as well as their clinical relevance. The important feature of NK cells is their inability to kill normal cells, while they are highly cytotoxic for infected or transformed cells. This discrimination has been largely resolved by the discovery of both activating and inhibitory receptors on NK cells and corresponding ligands on target cells. This review focuses briefly on several issues related to NK cells: (1) the phenotypic properties of NK cells, (2) the heterogeneity of NK cell activities, (3) the determination of three major NK subsets (Free, Binder, and Killer), (4) the maturation and activation of NK subsets, (5) the response of NK cells to various cytokines, (6) the target-induced inactivation and cell death of NK cells, (7) the multiple mechanisms of cell-mediated cytotoxicity, (8) the characterization of NK cytotoxic factors (NKCF), and (9) the role of membrane fluidity in cytotoxicity. These subjects are described chronologically beginning shortly after the discovery of NK cells as a result of Ron Herberman's leadership, and I am gratefully indebted to him.