Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, CH-8057 Zürich, Switzerland.
J Immunol. 2013 Nov 15;191(10):4989-95. doi: 10.4049/jimmunol.1301046. Epub 2013 Oct 9.
NK cells constitute the first line of defense against pathogens and transformed cells. They mature in secondary lymphoid organs, including tonsils, where common pathogens, such as EBV, enter the host and potentially imprint differentiating cells, which then patrol the body via the blood stream. Therefore, we set out to characterize a distinct human NK cell population in tonsils that produces high amounts of the immunomodulatory and antiviral cytokine IFN-γ. We found that the tonsilar IFN-γ(high) NK cell subset is CD56(bright)NKG2A(+)CD94(+)CD54(+)CD62L(-), is present in tonsils ex vivo and is more mature than other CD56(bright) NK cells in tonsils and less mature than other NK cells in blood, shows very low plasticity even after prolonged cytokine stimulation, accumulates in tonsils of EBV carriers, and is able to potently restrict EBV-induced transformation of B cells. Thus, we characterized a distinct and stable IFN-γ(high) NK cell subpopulation that can specifically restrict malignant transformation of EBV-infected B cells. This subset should be exploited for future development of cell-based therapeutic approaches in EBV-associated malignancies.
自然杀伤 (NK) 细胞构成了抵御病原体和转化细胞的第一道防线。它们在次级淋巴器官中成熟，包括扁桃体，常见病原体如 EBV 进入宿主并可能对分化细胞进行印记，然后通过血液在体内巡逻。因此，我们着手表征扁桃体中产生大量免疫调节和抗病毒细胞因子 IFN-γ 的独特人类 NK 细胞群体。我们发现扁桃体 IFN-γ(高)NK 细胞亚群是 CD56(bright)NKG2A(+)CD94(+)CD54(+)CD62L(-)，存在于扁桃体 ex vivo 中，比扁桃体中的其他 CD56(bright)NK 细胞更成熟，比血液中的其他 NK 细胞更不成熟，即使经过长时间的细胞因子刺激，其可塑性也非常低，在 EBV 携带者的扁桃体中积累，并能够有效地限制 EBV 诱导的 B 细胞转化。因此，我们表征了一种独特且稳定的 IFN-γ(高)NK 细胞亚群，能够特异性限制 EBV 感染的 B 细胞的恶性转化。该亚群应该被利用来开发针对 EBV 相关恶性肿瘤的基于细胞的治疗方法。
