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首页> 外文期刊>Nature immunology >Early specification of CD8+ T lymphocyte fates during adaptive immunity revealed by single-cell gene-expression analyses
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Early specification of CD8+ T lymphocyte fates during adaptive immunity revealed by single-cell gene-expression analyses

机译：单细胞基因表达分析揭示了适应性免疫过程中CD8 + T淋巴细胞命运的早期特征

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摘要

During microbial infection, responding T lymphocytes give rise to two distinct classes of cellular progeny: effector cells that provide acute host defense, and long-lived memory cells that provide durable immunity1. Terminally differentiated, short-lived effector T cells (Tsle cells) can be identified phenotypically by their high expression of the lectin-like receptor KLRG1 and low expression of the receptor for interleukin 7 (IL-7R)2. At least two distinct subsets of long-lived memory cells, central memory T cells (TcM cells) and effector memory T cells (TEM cells), have been described; these can be distinguished on the basis of their proliferative capacity, cytotoxicity, anatomic localization and expression of certain homing and chemokine receptors, including L-selectin (CD62L) and CCR7 (refs. 3,4).Published studies using single-cell adoptive transfer and 'genetic barcoding' approaches5'6 have demonstrated that a single naive CD8+ T lymphocyte can give rise to cells with more than one fate and, notably, is able to generate all of the diverse cellular fates necessary for an immune response. The process by which a single activated T lymphocyte yields effector- and memory-fated progeny and the time at which those differentiation pathways begin to diverge, however, remain unresolved. One possibility is that the progeny of an activated naive CD8+ T lymphocyte progress along a linear differentiation path, initially becoming effector cells, with a subset of those cells later acquiring the memory fate. An alternative possibility is that the first CD8+ T cell division in vivo is asymmetric9'10 and thus enables lymphocyte fates to diverge early during an immune response owing to unequal inheritance of certain determinants, such as the receptor for interferon-y (IFN-y) and the transcription factor T-bet.
机译：在微生物感染过程中，响应的T淋巴细胞产生两种不同的细胞后代：提供急性宿主防御的效应细胞和提供持久免疫力的长寿命记忆细胞1。可以通过表型上的凝集素样受体KLRG1的高表达和白介素7（IL-7R）2的受体的低表达来表型鉴定终末分化的，短暂的效应T细胞（Tsle细胞）。已经描述了长寿命记忆细胞的至少两个截然不同的子集，即中央记忆T细胞（TcM细胞）和效应记忆T细胞（TEM细胞）。这些可以根据它们的增殖能力，细胞毒性，解剖定位以及某些归巢和趋化因子受体（包括L-选择素（CD62L）和CCR7）的表达来区分（参考文献3,4）。 “遗传条形码”和“基因条形码”方法5'6已证明，单个幼稚的CD8 + T淋巴细胞可以产生具有多种命运的细胞，并且特别是能够产生免疫应答所需的所有各种细胞命运。但是，单个活化的T淋巴细胞产生效应子和记忆命运的后代的过程以及这些分化途径开始分化的时间仍然没有解决。一种可能性是，激活的天然CD8 + T淋巴细胞的后代沿着线性分化路径前进，最初成为效应细胞，而这些细胞的一部分后来获得了记忆。一种替代的可能性是，体内的首个CD8 + T细胞分裂是不对称的9'10，因此由于某些决定因素（如干扰素γ（IFN-y）的受体）遗传不均，使得淋巴细胞的命运在免疫反应过程中尽早发散。和转录因子T-bet。

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