Center for Virology and Vaccine Research (CVVR), Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts, United States.
Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, United States.
PLoS Pathog. 2018 May 31;14(5):e1007104. doi: 10.1371/journal.ppat.1007104. eCollection 2018 May.
Natural killer (NK) cells classically typify the nonspecific effector arm of the innate immune system, but have recently been shown to possess memory-like properties against multiple viral infections, most notably CMV. Expression of the activating receptor NKG2C is elevated on human NK cells in response to infection with CMV as well as HIV, and may delineate cells with memory and memory-like functions. A better understanding of how NKG2C+ NK cells specifically respond to these pathogens could be significantly advanced using nonhuman primate (NHP) models but, to date, it has not been possible to distinguish NKG2C from its inhibitory counterpart, NKG2A, in NHP because of unfaithful antibody cross-reactivity. Using novel RNA-based flow cytometry, we identify for the first time true memory NKG2C+ NK cells in NHP by gene expression (KLRC2), and show that these cells have elevated frequencies and diversify their functional repertoire specifically in response to rhCMV and SIV infections.
自然杀伤 (NK) 细胞经典地代表了先天免疫系统的非特异性效应臂，但最近已被证明对多种病毒感染具有类似记忆的特性，尤其是 CMV。在感染 CMV 和 HIV 后，人类 NK 细胞上激活受体 NKG2C 的表达升高，并且可能描绘具有记忆和类似记忆功能的细胞。更好地了解 NKG2C+ NK 细胞如何特异性地对这些病原体作出反应，可以通过非人类灵长类动物 (NHP) 模型得到显著推进，但迄今为止，由于抗体交叉反应不忠实，还不可能在 NHP 中区分 NKG2C 与其抑制性对应物 NKG2A。使用新的基于 RNA 的流式细胞术，我们首次通过基因表达 (KLRC2) 鉴定出 NHP 中的真正记忆 NKG2C+ NK 细胞，并表明这些细胞的频率升高，并专门针对 rhCMV 和 SIV 感染多样化其功能库。
