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【进展】Natu回复: 揭开NK细胞的新特征

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上次有个战友说用信号转导方面的理论来阐述免疫学问题,很容易发文章,而且发大文章。我也感觉这样的文章很悬乎,很高深。那么些通路纵横交错,置身其中,不知身在何处。但是看看此文,不由佩服研究者在解决一个很基础的理论问题时,其构思之巧妙,真是匠心独运。这篇文章思考问题的角度、解决问题的技巧、分析问题的深度,都值得我们作为经典文献来学习。

Nature 457, 557-561 (29 January 2009)
Adaptive immune features of natural killer cells
Joseph C. Sun1, Joshua N. Beilke1 & Lewis L. Lanier1
Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco, California 94143, USA

In an adaptive immune response, naive T cells proliferate during infection and generate long-lived memory cells that undergo secondary expansion after a repeat encounter with the same pathogen. Although natural killer (NK) cells have traditionally been classified as cells of the innate immune system, they share many similarities with cytotoxic T lymphocytes. We use a mouse model of cytomegalovirus infection to show that, like T cells, NK cells bearing the virus-specific Ly49H receptor proliferate 100-fold in the spleen and 1,000-fold in the liver after infection. After a contraction phase, Ly49H-positive NK cells reside in lymphoid and non-lymphoid organs for several months. These self-renewing 'memory' NK cells rapidly degranulate and produce cytokines on reactivation. Adoptive transfer of these NK cells into naive animals followed by viral challenge results in a robust secondary expansion and protective immunity. These findings reveal properties of NK cells that were previously attributed only to cells of the adaptive immune system.

内容简介

自然杀伤细胞(Natural killer cells)在适应性免疫应答中的性征

众所周知,在适应性免疫针对感染产生应答的过程中,初始T细胞(naive T cell)增殖形成细胞毒性T淋巴细胞(cytotoxic T lymphocyte,CTL),并生成长期存活的记忆性细胞,再次遇到相同病原体时产生二次扩增。这是适应性免疫应答的特征之一。通常,我们把自然杀伤细胞(NK cell)划归固有免疫系统,称其为机体细胞免疫的第一道屏障。本文研究表明,除了在固有免疫应答中发挥作用外,在适应性免疫应答中,NK细胞具有许多与CTL相似的特征。

通过采用巨细胞病毒(Cytomeglovirus)模型鼠,其NK细胞表面荷载病毒特异性受体Ly49H。病毒(MCMV )感染后,病毒特异性NK在脾脏(100倍)和肝脏(1000倍)发生增殖,与T细胞发生的增殖反应相似。之后,Ly49H阳性NK细胞进入淋巴样和非淋巴样器官,驻留长达数月。再次应答时,这些具有自我更新能力的记忆性NK细胞可快速脱颗粒并产生细胞因子。富集Ly49H阳性NK细胞输入新生小鼠体内,对相应病毒感染产生剧烈的细胞扩增和保护性免疫。

本研究表明,NK细胞具有适应性免疫应答相关性征,具体表现在具有免疫记忆的特点。NK细胞的生发,分类,功能定位和转归需要重新审视,有望成为新的焦点。

图片摘自Nature同期述评:《Immunology: Natural killer cells remember》by Sophie Ugolini1 & Eric Vivier1
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