Verstrepen B E, Nieuwenhuis I G, Mooij P, Bogers W M, Boonstra A, Koopman G
Department of Virology, Biomedical Primate Research Centre, Rijswijk, the Netherlands.
Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.
Clin Exp Immunol. 2016 Jul;185(1):42-9. doi: 10.1111/cei.12774. Epub 2016 Apr 27.
In humans, CD16 and CD56 are used to identify functionally distinct natural killer (NK) subsets. Due to ubiquitous CD56 expression, this marker cannot be used to distinguish between NK cell subsets in chimpanzees. Therefore, functional analysis of distinct NK subsets during hepatitis C virus (HCV) infection has never been performed in these animals. In the present study an alternative strategy was used to identify four distinct NK subsets on the basis of the expression of CD16 and CD94. The expression of activating and inhibiting surface receptors showed that these subsets resemble human NK subsets. CD107 expression was used to determine degranulation of the different subsets in naive and HCV-infected chimpanzees. In HCV-infected chimpanzees increased spontaneous cytotoxicity was observed in CD94(high/dim) CD16(pos) and CD94(low) CD16(pos) subsets. By contrast, increased natural cytotoxicity receptor (NCR)- mediated degranulation after NKp30 and NKp44 triggering was demonstrated in the CD94(dim) CD16(neg) subset. Our findings suggest that spontaneous and NCR-mediated cytotoxicity are effector functions of distinct NK subsets in HCV-infected chimpanzees.
在人类中，CD16和CD56用于识别功能不同的自然杀伤（NK）细胞亚群。由于CD56表达普遍存在，该标志物无法用于区分黑猩猩中的NK细胞亚群。因此，从未在这些动物中对丙型肝炎病毒（HCV）感染期间不同NK亚群进行功能分析。在本研究中，采用了一种替代策略，基于CD16和CD94的表达来识别四个不同的NK亚群。激活和抑制性表面受体的表达表明，这些亚群类似于人类NK亚群。利用CD107表达来确定未感染和HCV感染的黑猩猩中不同亚群的脱颗粒情况。在HCV感染的黑猩猩中，在CD94（高/低）CD16（阳性）和CD94（低）CD16（阳性）亚群中观察到自发细胞毒性增加。相比之下，在CD94（低）CD16（阴性）亚群中，NKp30和NKp44触发后自然细胞毒性受体（NCR）介导的脱颗粒增加。我们的研究结果表明，自发和NCR介导的细胞毒性是HCV感染的黑猩猩中不同NK亚群的效应功能。
