Arapović Maja, Brizić Ilija, Popović Branka, Jurković Slaven, Jordan Stefan, Krmpotić Astrid, Arapović Jurica, Jonjić Stipan
Department of Histology and Embryology, Faculty of Medicine, University of Rijeka , Rijeka , Croatia.
Center for Proteomics, Faculty of Medicine, University of Rijeka , Rijeka , Croatia.
Front Immunol. 2016 Apr 6;7:133. doi: 10.3389/fimmu.2016.00133. eCollection 2016.
In addition to their role as effector cells in virus control, natural killer (NK) cells have an immunoregulatory function in shaping the antiviral T-cell response. This function is further pronounced in perforin-deficient mice that show the enhanced NK-cell proliferation and cytokine secretion upon mouse cytomegalovirus (MCMV) infection. Here, we confirmed that stronger activation and maturation of NK cells in perforin-deficient mice correlates with higher MCMV load. To further characterize the immunoregulatory potential of perforin, we compared the response of NK cells that express or do not express perforin using bone-marrow chimeras. Our results demonstrated that the enhanced proliferation and maturation of NK cells in MCMV-infected bone-marrow chimeras is an intrinsic property of perforin-deficient NK cells. Thus, in addition to confirming that NK-cell proliferation is virus load dependent, our data extend this notion demonstrating that perforin plays an intrinsic role as a feedback mechanism in the regulation of NK-cell proliferation during viral infections.
除了作为控制病毒的效应细胞发挥作用外，自然杀伤（NK）细胞在塑造抗病毒T细胞反应方面具有免疫调节功能。在穿孔素缺陷小鼠中，这种功能更为明显，这些小鼠在感染小鼠巨细胞病毒（MCMV）后显示出NK细胞增殖增强和细胞因子分泌增加。在这里，我们证实穿孔素缺陷小鼠中NK细胞更强的激活和成熟与更高的MCMV载量相关。为了进一步表征穿孔素的免疫调节潜力，我们使用骨髓嵌合体比较了表达或不表达穿孔素的NK细胞的反应。我们的结果表明，MCMV感染的骨髓嵌合体中NK细胞增殖和成熟的增强是穿孔素缺陷NK细胞的固有特性。因此，除了证实NK细胞增殖依赖于病毒载量外，我们的数据扩展了这一概念，表明穿孔素在病毒感染期间作为调节NK细胞增殖的反馈机制发挥固有作用。
