HLA-DR(+) NK cells are mostly characterized by less mature phenotype and high functional activity.

HLA-DR(+) NK cells are mostly characterized by less mature phenotype and high functional activity.
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DOI:
10.1111/imcb.1032
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发表时间:
2018-03
影响因子:
4
通讯作者:
Kovalenko EI
Kovalenko EI
中科院分区:
医学3区
文献类型:
--
作者:
Erokhina SA;Streltsova MA;Kanevskiy LM;Telford WG;Sapozhnikov AM;Kovalenko EI

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NK细胞在激活过程中会改变其表型和功能特性。本研究旨在探讨人类白细胞抗原-DR的表达与NK细胞分化程度和功能活性的关系,并以表达IL-21的K562细胞(K562-mbIL21)为靶细胞,体外用IL-2刺激NK细胞。这种刺激技术已被描述为临床使用的NK细胞扩增。我们观察到,在新鲜分离的循环NK细胞中,HLADR的表达主要与分化较差的CD56brightCD57CD57−细胞有关,但在一些个体中也可以在终末分化的CD57+细胞中发现。体外培养的HLADR+NK细胞在细胞因子刺激下产生干扰素γ的能力强于HLADR−细胞。在体外,IL-2和K562-mBIL21激活可增加CD56brightCD57−NK细胞中HLADR阳性的NK细胞比例。这尤其是由于在人类白细胞抗原DR阴性细胞中出现了人类白细胞抗原DR+的从头表达。在体外获得的HLADR表达与NK细胞增殖活性、细胞因子诱导的干扰素-γ产生增加、滋养细胞脱颗粒增加、CD86NKG2D高表达有关。因此,在NK细胞的激活和扩增过程中,IL-2/K562-mbIL21的刺激会引起明显的表型和功能变化。
NK cells change their phenotype and functional characteristics during activation. In this work, we searched for a relationship of HLA-DR expression with differentiation stages and functional activity of NK cells ex vivo and stimulated in vitro with IL-2 challenged with gene modified feeder K562 cells expressing membrane-bound IL-21 (K562-mbIL21). This stimulation technique has been described for NK cell expansion in clinical use. We have observed that HLA-DR expression in freshly isolated circulating NK cells was mostly associated with less differentiated CD56brightCD57− cells, although in some individuals it could also be found in terminally differentiated CD57+ cells. Ex vivo HLA-DR+ NK cells possessed better capacity to produce IFN-γ in response to cytokine stimulation compared to their HLA-DR− counterparts. In vitro activation with IL-2 and K562-mbIL21 induces an increase in HLA-DR-positive NK cell proportion, again mostly among CD56brightCD57− NK cells. This happened in particular due to appearance of HLA-DR+ expression de novo in HLA-DR-negative cells. Acquired in vitro HLA-DR expression was associated with NK cell proliferation activity, more intense cytokine-induced IFN-γ production, increased degranulation toward feeder cells, and higher expression of CD86 and NKG2D. Thus, stimulation with IL-2/K562-mbIL21 causes a significant phenotype and functional shift during NK cell activation and expansion.
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