Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany; Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45147, Germany.
Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
Immunity. 2014 Jun 19;40(6):949-60. doi: 10.1016/j.immuni.2014.05.004. Epub 2014 Jun 5.
Despite development of new antiviral drugs, viral infections are still a major health problem. The most potent antiviral defense mechanism is the innate production of type I interferon (IFN-I), which not only limits virus replication but also promotes antiviral T cell immunity through mechanisms, which remain insufficiently studied. Using the murine lymphocytic choriomeningitis virus model system, we show here that IFN-I signaling on T cells prevented their rapid elimination in vivo. Microarray analyses uncovered that IFN-I triggered the expression of selected inhibitory NK-cell-receptor ligands. Consequently, T cell immunity of IFN-I receptor (IFNAR)-deficient T cells could be restored by NK cell depletion or in NK-cell-deficient hosts (Nfil3(-/-)). The elimination of Ifnar1(-/-) T cells was dependent on NK-cell-mediated perforin expression. In summary, we identified IFN-I as a key player regulating the protection of T cells against regulatory NK cell function.
尽管开发了新的抗病毒药物，但病毒感染仍然是一个主要的健康问题。最有效的抗病毒防御机制是 I 型干扰素（IFN-I）的先天产生，它不仅限制了病毒的复制，而且通过仍未充分研究的机制促进抗病毒 T 细胞免疫。在这里，我们使用鼠淋巴细胞脉络丛脑膜炎病毒模型系统表明，IFN-I 信号在 T 细胞上防止了它们在体内的快速消除。微阵列分析揭示了 IFN-I 触发了选定的抑制性 NK 细胞受体配体的表达。因此，IFNAR 缺陷 T 细胞的 T 细胞免疫可以通过 NK 细胞耗竭或在 NK 细胞缺陷宿主（Nfil3(-/-)）中恢复。Ifnar1(-/-) T 细胞的消除依赖于 NK 细胞介导的穿孔素表达。总之，我们确定 IFN-I 是调节 T 细胞对抗调节性 NK 细胞功能的保护的关键因素。
