IL-21 induces the functional maturation of murine NK cells
IL-21 induces the functional maturation of murine NK cells
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DOI：
10.4049/jimmunol.172.4.2048
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发表时间：
2004-02-15
影响因子：
4.4
通讯作者：
Nutt, SL
中科院分区：
文献类型：
--
作者：
Brady, J;Hayakawa, Y;Nutt, SL
IL-21是最近鉴定的在体外刺激小鼠NK细胞效应子功能的细胞因子。在这项研究中，我们证明，IL-21通过诱导成熟NK细胞发育成具有增强效应子功能的大颗粒淋巴细胞表型来实现其刺激作用。IL-21处理导致细胞大小和粒度增加以及细胞活力和增殖潜力的相应降低。这些细胞上调抑制性CD 94-NKG 2A受体复合物和激活标志物CD 154以及杀伤细胞、凝集素样受体G1的表达。令人惊讶的是，IL-21处理也导致泛NK标志物NK1.1的下调。与这些细胞变化相一致，IL-21增强了跨一系列靶敏感性的细胞溶解能力，并诱导IL-10和IFN-γ产生。用IL-21的体内治疗导致NK细胞的非常相似的活化和表型成熟以及NK细胞介导的抗肿瘤免疫力的有效增加，其是穿孔素依赖性的。这些发育变化表明，IL-21的功能是诱导小鼠NK细胞的终末分化，导致NK细胞介导的细胞毒性和免疫监视增强。
IL-21 is a recently identified cytokine that stimulates mouse NK cell effector functions in vitro. In this study we demonstrate that IL-21 achieves its stimulatory effect by inducing the development of mature NK cells into a large granular lymphocyte phenotype with heightened effector function. IL-21 treatment results in increased cell size and granularity and a corresponding decrease in cell viability and proliferative potential. These cells up-regulate the expression of the inhibitory CD94-NKG2A receptor complex and the activation markers CD154 and killer cell, lectin-like-receptor G1. Surprisingly, IL-21 treatment also results in down-regulation of the pan-NK marker, NK1.1. Coinciding with these cellular changes IL-21 enhances cytolytic capacity across a spectrum of target sensitivities and induces IL-10 and IFN-gamma production. In vivo treatment with IL-21 results in a very similar activation and phenotypic maturation of NK cells as well as a potent increase in NK cell-mediated anti-tumor immunity that is perforin dependent. These, developmental changes suggested that IL-21 functions to induce the terminal differentiation of mouse NK cells, resulting in heightened NK cell-mediated cytotoxicity and immune surveillance.