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离子霉素处理使自然杀伤细胞反应性降低。

Ionomycin Treatment Renders NK Cells Hyporesponsive.

作者信息

Romera-Cárdenas Gema, Thomas L Michael, Lopez-Cobo Sheila, García-Cuesta Eva M, Long Eric O, Reyburn Hugh T

机构信息

Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, CNB-CSIC, Madrid, Spain.

Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States of America.

出版信息

PLoS One. 2016 Mar 23;11(3):e0150998. doi: 10.1371/journal.pone.0150998. eCollection 2016.

DOI:10.1371/journal.pone.0150998
PMID:27007115
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4805247/
Abstract

Natural killer cells are cytotoxic lymphocytes important in immune responses to cancer and multiple pathogens. However, chronic activation of NK cells can induce a hyporesponsive state. The molecular basis of the mechanisms underlying the generation and maintenance of this hyporesponsive condition are unknown, thus an easy and reproducible mechanism able to induce hyporesponsiveness on human NK cells would be very useful to gain understanding of this process. Human NK cells treated with ionomycin lose their ability to degranulate and secrete IFN-γ in response to a variety of stimuli, but IL-2 stimulation can compensate these defects. Apart from reductions in the expression of CD11a/CD18, no great changes were observed in the activating and inhibitory receptors expressed by these NK cells, however their transcriptional signature is different to that described for other hyporesponsive lymphocytes.

摘要

自然杀伤细胞是细胞毒性淋巴细胞,在对癌症和多种病原体的免疫反应中起重要作用。然而,自然杀伤细胞的慢性激活可诱导低反应状态。这种低反应状态产生和维持机制的分子基础尚不清楚,因此,一种能够诱导人自然杀伤细胞低反应性的简便且可重复的机制,对于了解这一过程将非常有用。用离子霉素处理的人自然杀伤细胞失去了对多种刺激脱颗粒和分泌干扰素-γ的能力,但白细胞介素-2刺激可弥补这些缺陷。除了CD11a/CD18表达降低外,这些自然杀伤细胞表达的激活和抑制受体没有观察到太大变化,然而它们的转录特征与其他低反应性淋巴细胞不同。

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NK-cell dysfunction in human renal carcinoma reveals diacylglycerol kinase as key regulator and target for therapeutic intervention.
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