Multiple effects of IL-21 on human NK cells in ex vivo expansion
Multiple effects of IL-21 on human NK cells in ex vivo expansion
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DOI：
10.1016/j.imbio.2015.01.009
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发表时间：
2015-07-01
期刊：
影响因子：
2.8
通讯作者：
Huang, Qing-Sheng
中科院分区：
文献类型：
--
作者：
Li, Qi;Ye, Lin-Jie;Huang, Qing-Sheng
自然杀伤（NK）细胞（CD 56（+）CD 3（-））是大的颗粒状免疫细胞，在抗炎反应和肿瘤监测中发挥非常关键的作用。NK细胞作为一种理想的细胞毒性淋巴细胞（CTL），在临床试验中备受关注。然而，数量不足和寿命有限是限制NK细胞在过继免疫治疗中应用的瓶颈。白细胞介素如IL-2、IL-15和IL-18被认为是刺激NK细胞的因子，并已用于NK细胞离体扩增。与IL-2和IL-15类似，IL-21是一种常见的γ链细胞因子，在NK细胞活化、成熟和增殖中很重要。本研究旨在评估膜结合和可溶性IL-21对原代人NK细胞体外扩增的影响。发现IL-21对NK细胞具有多种作用，通过上调IFN-γ和颗粒酶-B表达以浓度依赖性方式增加其细胞毒性。然而，在高浓度（50 ng/mL）下，IL-21通过显著诱导凋亡缩短NK细胞的寿命。此外，当用IL-21处理时，在离体扩增期间，外周血单核细胞（PBMC）中的NKT（CD 56（+）CD 3（+））细胞的数量以浓度依赖性方式增加。IL-21还促进扩增的细胞在培养的第一至第二周进入细胞周期的S期。所有这些结果表明，IL-21对NK细胞的发育和功能具有多重作用。IL-21用于NK细胞体外扩增时应注意其剂量和多重效应。(C)2015 Elsevier GmbH. All rights reserved.
Natural killer (NK) cells (CD56(+)CD3(-)) are large, granular immunocytes that play a very pivotal role in the anti-inflammatory response and tumor surveillance. As an ideal cytotoxic lymphocyte (CTL), NK cells have attracted much attention in clinical trials. However, an insufficient number and their limited life span are bottlenecks that limit the application of NK cells in adoptive immunotherapy. Interleukins such as IL-2, IL-15 and IL-18 are recognized as factors that stimulate NK cells and have been used in NK cells ex vivo expansion. Similar to IL-2 and IL-15, IL-21 is a common gamma-chain cytokine that is important in NK cell activation, maturation and proliferation. The present study aims to assess the effects of membrane-bound and soluble IL-21 on primary human NK cells during ex vivo expansion. IL-21 was found to have multiple effects on NK cells, increasing their cytotoxicity in a concentration-dependent manner by up-regulating IFN-gamma and Granzyme-B expression. Nevertheless, at a high concentration (50 ng/mL), IL-21 curtailed the life span of NK cells by significantly inducing apoptosis. Moreover, when treated with IL-21, the number of NKT (CD56(+)CD3(+)) cells increased among peripheral blood mononuclear cells (PBMCs) during ex vivo expansion in a concentration-dependent manner. IL-21 also promoted expanded cells to enter into S phase of the cell cycle during the first to second weeks of culture. All these results suggest that IL-21 has multiple effects on NK cell development and functions. More attention should be given to the dosage and multiple effects of IL-21 when it was applied to NK cells in ex vivo expansion. (C) 2015 Elsevier GmbH. All rights reserved.