CD56-negative NK cells: Frequency in peripheral blood, expansion during HIV-1 infection, functional capacity, and KIR expression.

CD56-negative NK cells: Frequency in peripheral blood, expansion during HIV-1 infection, functional capacity, and KIR expression.
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DOI:
10.3389/fimmu.2022.992723
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发表时间:
2022
影响因子:
7.3
通讯作者:
Parham, Peter
Parham, Peter
中科院分区:
医学2区
文献类型:
--
作者:
Cocker, Alexander T. H.;Liu, Fuguo;Djaoud, Zakia;Guethlein, Lisbeth A. A.;Parham, Peter

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人类NK细胞通常定义为CD 3-CD 56+淋巴细胞。然而,显示NK相关标志物的CD 56-CD 16+(CD 56阴性)淋巴细胞群体在慢性病毒感染(如HIV-1和HCV)期间扩增,在疱疹病毒感染中扩增程度较低。这种CD 56阴性NK细胞亚群尚未得到充分研究,因为它需要排除其他淋巴细胞才能准确识别其存在。关于CD 56阴性NK细胞群体的起源、发育、表型和功能仍存在许多问题。我们的目的是通过进行荟萃分析来确定健康对照中该NK亚群的频率及其在病毒感染中的变化。除此之外,我们还分析了储存的CyTOF和scRNAseq数据集,以确定CD 56阴性NK细胞群体的表型和亚群,以及它们的功能变异。我们在来自28项研究和6个数据集的757名个体中发现,CD 56阴性亚群占健康外周血中NK细胞的5.67%,而HIV-1感染使这一群体增加了10.69%的平均差异。NK亚群之间表面标志物表达的荟萃分析显示,CD 56阴性亚群内没有证据表明耗竭增加或增殖减少。CD 56阴性NK细胞具有独特的KIR表达模式,这意味着它们具有KIR介导的教育的独特潜力。与其他CD 56阴性细胞相比,穿孔素-CD 94-NKG 2C-NKp 30-CD 56阴性细胞群对K562细胞表现出不同的基因表达和脱粒反应。该分析区分了CD 56阴性NK细胞的两个功能不同的亚群。他们是表型多样的,并有不同的能力,教育HLA I类与KIR的相互作用。
Human NK cells are usually defined as CD3-CD56+ lymphocytes. However, a CD56-CD16+ (CD56neg) lymphocyte population that displays NK-associated markers expands during chronic viral infections such as HIV-1 and HCV, and, to lesser extent, in herpesvirus infections. This CD56neg NK cell subset has been understudied because it requires the exclusion of other lymphocytes to accurately identify its presence. Many questions remain regarding the origin, development, phenotype, and function of the CD56neg NK cell population. Our objective was to determine the frequency of this NK subset in healthy controls and its alteration in viral infections by performing a meta-analysis. In addition to this, we analyzed deposited CyTOF and scRNAseq datasets to define the phenotype and subsets of the CD56neg NK cell population, as well as their functional variation. We found in 757 individuals, from a combined 28 studies and 6 datasets, that the CD56neg subset constitutes 5.67% of NK cells in healthy peripheral blood, while HIV-1 infection increases this population by a mean difference of 10.69%. Meta-analysis of surface marker expression between NK subsets showed no evidence of increased exhaustion or decreased proliferation within the CD56neg subset. CD56neg NK cells have a distinctive pattern of KIR expression, implying they have a unique potential for KIR-mediated education. A perforin-CD94-NKG2C-NKp30- CD56neg population exhibited different gene expression and degranulation responses against K562 cells compared to other CD56neg cells. This analysis distinguishes two functionally distinct subsets of CD56neg NK cells. They are phenotypically diverse and have differing capacity for education by HLA class-I interactions with KIRs.
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