Li Tingting, Wang Jian, Wang Yanshi, Chen Yongyan, Wei Haiming, Sun Rui, Tian Zhigang
The Chinese Academy of Sciences Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China; and.
The Chinese Academy of Sciences Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China; and
J Immunol. 2017 Feb 1;198(3):1242-1252. doi: 10.4049/jimmunol.1502186. Epub 2016 Dec 28.
Although NK cells are classified as innate immune cells, recent studies have demonstrated the transformation of NK cells into long-lived memory cells that contribute to secondary immune responses in certain mouse models. However, whether NK cells mount an Ag-specific memory response to acute influenza virus infection has not yet been examined. Here, we show that, consistent with previous studies, lung NK cells play an important role in controlling viral proliferation after primary influenza virus infection. However, although lung NK cells display a memory phenotype at the late stage of infection, these cells do not protect mice against secondary influenza virus infection. Interestingly, liver NK cells from influenza virus-infected mice possess a memory phenotype and protect mice against secondary influenza virus infection. Memory-like liver NK cells display a CD49aDX5 phenotype, and the adoptive transfer of purified liver CD49aDX5 NK cells into naive mice followed by viral infection results in protective immunity and decreased viral titer. Moreover, we demonstrate that primary inactivated influenza virus induces memory NK cells residing in the liver of Rag1 mice. Collectively, these data suggest that liver CD49aDX5 NK cells remember encountered Ag from influenza virus after primary infection and are more protective upon subsequent infection.
尽管自然杀伤（NK）细胞被归类为先天免疫细胞，但最近的研究表明，在某些小鼠模型中，NK细胞可转变为长寿记忆细胞，有助于二次免疫反应。然而，NK细胞是否会对急性流感病毒感染产生抗原特异性记忆反应尚未得到研究。在此，我们表明，与先前的研究一致，肺NK细胞在初次流感病毒感染后控制病毒增殖中起重要作用。然而，尽管肺NK细胞在感染后期表现出记忆表型，但这些细胞并不能保护小鼠免受二次流感病毒感染。有趣的是，来自流感病毒感染小鼠的肝脏NK细胞具有记忆表型，并能保护小鼠免受二次流感病毒感染。记忆样肝脏NK细胞表现出CD49aDX5表型，将纯化的肝脏CD49aDX5 NK细胞过继转移到未感染的小鼠中，随后进行病毒感染，可产生保护性免疫并降低病毒滴度。此外，我们证明，初次灭活流感病毒可诱导Rag1小鼠肝脏中的记忆NK细胞。总体而言，这些数据表明，肝脏CD49aDX5 NK细胞在初次感染后记住了来自流感病毒的抗原，并且在随后的感染中具有更强的保护作用。
