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Regulation of NK cell responsiveness to achieve self-tolerance and maximal responses to diseased target cells.
Immunological Reviews ( IF 7.5 ) Pub Date : 2008-08-01 , DOI: 10.1111/j.1600-065x.2008.00658.x
Nathalie T Joncker 1 , David H Raulet
Affiliation  

Inhibitory receptors specific for major histocompatibility complex (MHC) class I molecules govern the capacity of natural killer (NK) cells to attack class I-deficient cells ('missing-self recognition'). These receptors are expressed stochastically, such that the panel of expressed receptors varies between NK cells. This review addresses how the activity of NK cells is coordinated in the face of this variation to achieve a repertoire that is self-tolerant and optimally reactive with diseased cells. Recent studies show that NK cells arise in normal animals or humans that lack any known inhibitory receptors specific for self-MHC class I. These NK cells exhibit self-tolerance and exhibit functional hyporesponsiveness to stimulation through various activating receptors. Evidence suggests that hyporesponsiveness is induced because these NK cells cannot engage inhibitory MHC class I molecules and are therefore persistently over-stimulated by normal cells in the environment. Finally, we discuss evidence that hyporesponsiveness is a quantitative trait that varies depending on the balance of signals encountered by developing NK cells. Thus, a tuning process determines the functional set-point of NK cells, providing a basis for discriminating self from missing-self, and at the same time endowing each NK cell with the highest inherent responsiveness compatible with self-tolerance.

中文翻译:

调节 NK 细胞反应性,以实现对患病靶细胞的自我耐受和最大反应。

主要组织相容性复合体 (MHC) I 类分子的特异性抑制性受体控制着自然杀伤 (NK) 细胞攻击 I 类缺陷细胞(“缺失自我识别”)的能力。这些受体是随机表达的,因此表达的受体组因 NK 细胞而异。这篇综述讨论了 NK 细胞的活性如何在这种变化下进行协调,以实现具有自我耐受性并与患病细胞具有最佳反应性的所有成分。最近的研究表明,NK 细胞存在于缺乏任何已知的针对自身 MHC I 类的抑制性受体的正常动物或人类中。这些 NK 细胞表现出自我耐受性,并对通过各种激活受体的刺激表现出功能性低反应性。有证据表明,由于这些 NK 细胞不能与抑制性 MHC I 类分子结合,因此会被环境中的正常细胞持续过度刺激,因此会诱发低反应性。最后,我们讨论了低反应性是一种数量性状的证据,它根据发育中的 NK 细胞遇到的信号平衡而变化。因此,调整过程决定了 NK 细胞的功能设定点,为区分自我和缺失自我提供了基础,同时赋予每个 NK 细胞与自我耐受相容的最高固有反应能力。我们讨论了低反应性是一种数量性状的证据,它根据发育中的 NK 细胞遇到的信号平衡而变化。因此,调整过程决定了 NK 细胞的功能设定点,为区分自我和缺失自我提供了基础,同时赋予每个 NK 细胞与自我耐受相容的最高固有反应能力。我们讨论了低反应性是一种数量性状的证据,它根据发育中的 NK 细胞遇到的信号平衡而变化。因此,调整过程决定了 NK 细胞的功能设定点,为区分自我和缺失自我提供了基础,同时赋予每个 NK 细胞与自我耐受相容的最高固有反应能力。
更新日期:2019-11-01
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