NKp46 expression discriminates porcine NK cells with different functional properties
NKp46 expression discriminates porcine NK cells with different functional properties
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DOI：
10.1002/eji.201141989
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发表时间：
2012-05-01
影响因子：
5.4
通讯作者：
Gerner, Wilhelm
中科院分区：
文献类型：
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作者：
Mair, Kerstin H.;Essler, Sabine E.;Gerner, Wilhelm
到目前为止，由于缺乏自然杀伤(NK)细胞特异性标记物，人们对猪的NK细胞知之甚少。在这项研究中，我们用新开发的单抗(MAbbs)鉴定了猪的激活受体NKp46(CD335)，以便对该物种的NK细胞进行更详细的研究。NKp46单抗与穿孔素+CD2+CD3-CD8a+CD16+淋巴细胞有明显的特异性反应。在脾和肝中，观察到NKp46表达增加的CD8adim/-淋巴细胞亚群。令人惊讶的是，我们可以在所有被分析的动物中发现具有NK细胞表型的NKp46-细胞。这些淋巴细胞对异种和同种异体靶细胞的杀伤活性与NKp46+NK细胞相当。相比之下，NKp46+NK细胞产生的干扰素水平高出数倍。(干扰素-？)细胞因子刺激后的NKp46-细胞。此外，在IL-2、IL-12和IL-18刺激后，NKp46-细胞中NKp46的表达可以被激活依赖地诱导。综上所述，我们的数据表明NKp46并不是所有的猪NK细胞都表达，并且NKp46在细胞因子产生方面区分不同的猪NK细胞，这对NKp46作为不同哺乳动物物种中NK细胞的综合标志物的范式提出了挑战。
So far little is known about natural killer (NK) cells in the pig due to the lack of NK cell-specific markers. In this study, we identified the activating receptor NKp46 (CD335) in swine with newly developed monoclonal antibodies (mAbs) for more detailed studies on NK cells in this species. The NKp46 mAbs showed a specific reactivity with a distinct population of perforin+CD2+CD3-CD8a+CD16+ lymphocytes. In spleen and liver, an additional subset of CD8adim/- lymphocytes with increased NKp46 expression was observed. Surprisingly, we could identify NKp46- cells with an NK cell phenotype in all animals analyzed. These lymphocytes showed comparable cytolytic activity against xenogeneic and allogeneic target cells as NKp46+ NK cells. In contrast, NKp46+ NK cells produced several fold higher levels of interferon-? (IFN-?) than the NKp46- cells after cytokine stimulation. Furthermore, an activation-dependent induction of NKp46 expression in formerly NKp46- cells after stimulation with interleukin-2 (IL-2), IL-12, and IL-18 could be shown. In summary, our data indicate that NKp46 is not expressed by all porcine NK cells and that NKp46 discriminates porcine NK cells differing in regard to cytokine production, which challenges the paradigm of NKp46 as a comprehensive marker for NK cells across different mammalian species.