Differential secretion of TNF-alpha and IFN-gamma by human peripheral blood-derived NK subsets and association with functional maturation
Differential secretion of TNF-alpha and IFN-gamma by human peripheral blood-derived NK subsets and association with functional maturation
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DOI：
10.1007/bf01540972
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发表时间：
1996-01-01
影响因子：
9.1
通讯作者：
Bonavida, B
中科院分区：
文献类型：
--
作者：
Jewett, A;Gan, XH;Bonavida, B
自然杀伤细胞可分为三个主要亚群(游离、结合。和杀手)基于它们结合和杀死敏感目标细胞的能力。无粘结剂、无杀伤性的细胞是最不成熟的，可以被激活成为粘结剂和杀手。自然杀伤(NK)细胞合成和分泌多种与NK激活密切相关的细胞因子。本研究观察纯化的NK细胞及其亚群在不同刺激条件下分泌肿瘤坏死因子-α(TNF-α)和干扰素-γ(干扰素-γ)的情况。K562靶细胞通过结合亚群和杀伤亚群刺激肿瘤坏死因子-α和干扰素-γ的分泌，但不能刺激游离亚群的分泌。干扰素-α只激活干扰素-γ的分泌，而IL-2通过结合子和杀伤亚群同时激活肿瘤坏死因子-α和干扰素-γ的分泌，K562的加入使细胞的分泌增加。佛波醇肉豆蔻酸酯(PMA)和离子载体刺激结合亚群和杀伤亚群的肿瘤坏死因子-α和干扰素-γ的分泌，但在结合亚群中干扰素-γ的分泌更为明显。活化的肿瘤坏死因子-α和干扰素-γ的分泌依赖于从头合成蛋白质。单细胞水平的分析表明，结合亚群分泌干扰素-γ的细胞频率最高。这些结果表明，结合亚群和杀伤亚群均可被激活以分泌肿瘤坏死因子-α和干扰素-γ，而游离NK亚群在激活后很少或根本不分泌肿瘤坏死因子-α和干扰素-γ。提示NK细胞活化后分泌肿瘤坏死因子-α和干扰素-γ的能力与NK细胞成熟的功能阶段有关。
Natural killer cells can be separated into three major subsets (free, binder. and killer) based on their ability to bind and kill sensitive target cells. The nonbinder, nonkiller free cells are the most immature and can be activated to become binders and killers. Natural killer (NK) cells synthesize and secrete several cytokines that are intimately involved in NK activation. This study investigated the secretion of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) by purified NK cells and NK subsets following activation by various stimuli. K562 target cells stimulated secretion of both TNF-alpha and IFN-gamma by both the binder and the killer subsets but not by the free subset. IFN-alpha activated the secretion of IFN-gamma only, whereas IL-2 activated the secretion of both TNF-alpha and IFN-gamma by the binder and killer subsets and secretion was augmented by the addition of K562 to the cultures. Phorbol myristate acetate (PMA) and ionophore stimulated TNF-alpha and IFN-gamma secretion in both the binder and the killer subsets, though IFN-gamma secretion was more pronounced in the binder subset. Activation of TNF-alpha and IFN-gamma secretion was dependent on de novo protein synthesis. Analysis at the single-cell level demonstrated that the binder subset had the highest frequency of cells secreting IFN-gamma. These results demonstrate that both the binder and the killer subsets can be activated to secrete TNF-alpha and IFN-gamma, whereas the free NK subset secretes little or no TNF-alpha and IFN-gamma following activation. These data suggest that the ability of NK cells to secrete TNF-alpha and IFN-gamma following activation correlates with the functional stage of maturation of NK cells.