Running to Stand Still: Naive CD8(+) T Cells Actively Maintain a Program of Quiescence.
Running to Stand Still: Naive CD8(+) T Cells Actively Maintain a Program of Quiescence.
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DOI：
10.3390/ijms21249773
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发表时间：
2020-12-21
影响因子：
5.6
通讯作者：
Turner SJ
中科院分区：
文献类型：
--
作者：
Bennett TJ;Udupa VAV;Turner SJ
CD8+ T细胞在清除细胞内病原体和对抗肿瘤中起着关键作用。感染后，naïve CD8+ T细胞分化为效应细胞和记忆细胞，染色质结构和基因表达的大规模和协调变化强调了这一程序。重要的是，最近的证据表明，调节记忆T细胞快速效应功能的表观遗传机制是先天免疫细胞（如自然杀伤（NK）细胞）共享的。因此，先天免疫和适应性免疫之间的关键区别似乎在于naïve状态的存在。这一重要的区别提出了一个有趣的新假设，即naïve状态是进化中安装的，用于抑制抗原识别反应中效应和记忆分化的默认程序。因此，我们认为适应性T免疫的标志是naïve程序，该程序主动维持CD8+ T细胞静止，直到收到适当的激活信号。在这篇综述中，我们研究了naïve CD8+ T细胞静止的机制控制，并总结了naïve细胞在限制自发和不适当激活时施加的多重抑制。这包括表观遗传机制和基因表达的转录因子（TF）调控，以及新的抑制受体、RNA丰度和蛋白质降解。
CD8+ T cells play a pivotal role in clearing intracellular pathogens and combatting tumours. Upon infection, naïve CD8+ T cells differentiate into effector and memory cells, and this program is underscored by large-scale and coordinated changes in the chromatin architecture and gene expression. Importantly, recent evidence demonstrates that the epigenetic mechanisms that regulate the capacity for rapid effector function of memory T cells are shared by innate immune cells such as natural killer (NK) cells. Thus, it appears that the crucial difference between innate and adaptive immunity is the presence of the naïve state. This important distinction raises an intriguing new hypothesis, that the naïve state was evolutionary installed to restrain a default program of effector and memory differentiation in response to antigen recognition. We argue that the hallmark of adaptive T immunity is therefore the naïve program, which actively maintains CD8+ T cell quiescence until receipt of appropriate activation signals. In this review, we examine the mechanistic control of naïve CD8+ T cell quiescence and summarise the multiple levels of restraint imposed in naïve cells in to limit spontaneous and inappropriate activation. This includes epigenetic mechanisms and transcription factor (TF) regulation of gene expression, in addition to novel inhibitory receptors, abundance of RNA, and protein degradation.
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DOI：
10.1084/jem.20021910
发表时间：
2003-05-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Curtsinger JM;Lins DC;Mescher MF
通讯作者：
Mescher MF
影响因子：
5.3
作者：
Firestein, R;Cui, XM;Cleary, ML
通讯作者：
Cleary, ML
影响因子：
64.8
作者：
Agger, Karl;Cloos, Paul A. C.;Helin, Kristian
通讯作者：
Helin, Kristian
影响因子：
16.8
作者：
Hamilton SE;Jameson SC
通讯作者：
Jameson SC
DOI：
10.4049/jimmunol.1402648
发表时间：
2015-06-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Flies DB;Higuchi T;Chen L
通讯作者：
Chen L