Traditionally, NK cells belong to the innate immune system and eliminate virus-infected cells through their germline-encoded receptors. However, NK cells were recently reported to possess memory-like functions that were predominantly provided by hepatic NK cells. Memory properties were mainly documented in contact hypersensitivity models or during cytomegalovirus infections. However, the precise role and the physiologic importance of memory-like NK cells during retroviral infections are still under investigation. Here, we show that Friend retrovirus (FV) infection of mice induced a population of phenotypically memory-like NK cells at 28 days post infection. Upon secondary antigen encounter, these NK cells showed an increased production of the pro-inflammatory cytokines IFNγ and TNFα as well as the death ligand FasL in comparison to naïve NK cells. Furthermore, we found an augmented elimination of antigen-matched but not antigen-mismatched target cells by these memory-like NK cells. In adoptive cell transfer experiments, equal antiviral activities of splenic and hepatic memory-like NK cells during the late phase of acute FV infection were found. Our results strongly imply the existence and antiviral activity of spleen and liver memory-like NK cells in FV infection, which efficiently respond upon secondary exposure to retroviral antigens.

中文翻译：

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朋友逆转录病毒感染诱导记忆样自然杀伤细胞的发育

传统上，NK 细胞属于先天免疫系统，通过其生殖系编码的受体消除病毒感染的细胞。然而，最近有报道称 NK 细胞具有主要由肝 NK 细胞提供的类似记忆的功能。记忆特性主要记录在接触超敏反应模型或巨细胞病毒感染期间。然而，记忆样 NK 细胞在逆转录病毒感染中的确切作用和生理重要性仍在研究中。在这里，我们展示了 Friend 逆转录病毒 (FV) 感染小鼠在感染后 28 天诱导了一群表型记忆样 NK 细胞。在遇到二次抗原时，与初始 NK 细胞相比，这些 NK 细胞显示出促炎细胞因子 IFNγ 和 TNFα 以及死亡配体 FasL 的产生增加。此外，我们发现这些记忆样 NK 细胞增强了消除抗原匹配但不是抗原错配的靶细胞。在过继细胞转移实验中，发现在急性 FV 感染晚期，脾和肝记忆样 NK 细胞具有相同的抗病毒活性。我们的结果强烈暗示脾脏和肝脏记忆样 NK 细胞在 FV 感染中的存在和抗病毒活性，它们在二次暴露于逆转录病毒抗原时有效地做出反应。