Institute of Microbiology, ETH Zürich, 8093 Zurich, Switzerland.
Vital-IT, Swiss Institute of Bioinformatics, CHUV, University of Lausanne, 1015 Lausanne, Switzerland.
Immunity. 2014 Jun 19;40(6):961-73. doi: 10.1016/j.immuni.2014.05.003. Epub 2014 Jun 5.
Direct type I interferon (IFN) signaling on T cells is necessary for the proper expansion, differentiation, and survival of responding T cells following infection with viruses prominently inducing type I IFN. The reasons for the abortive response of T cells lacking the type I IFN receptor (Ifnar1(-/-)) remain unclear. We report here that Ifnar1(-/-) T cells were highly susceptible to natural killer (NK) cell-mediated killing in a perforin-dependent manner. Depletion of NK cells prior to lymphocytic choriomeningitis virus (LCMV) infection completely restored the early expansion of Ifnar1(-/-) T cells. Ifnar1(-/-) T cells had elevated expression of natural cytotoxicity triggering receptor 1 (NCR1) ligands upon infection, rendering them targets for NCR1 mediated NK cell attack. Thus, direct sensing of type I IFNs by T cells protects them from NK cell killing by regulating the expression of NCR1 ligands, thereby revealing a mechanism by which T cells can evade the potent cytotoxic activity of NK cells.
直接的 I 型干扰素 (IFN) 信号通路对 T 细胞在病毒感染后的适当扩增、分化和存活是必要的，因为这些病毒会显著诱导 I 型 IFN 的产生。缺乏 I 型 IFN 受体 (Ifnar1(-/-)) 的 T 细胞反应为何会中断，其原因仍不清楚。我们在这里报告称，Ifnar1(-/-) T 细胞以依赖穿孔素的方式极易受到自然杀伤 (NK) 细胞介导的杀伤。在淋巴细胞脉络丛脑膜炎病毒 (LCMV) 感染前耗尽 NK 细胞可完全恢复 Ifnar1(-/-) T 细胞的早期扩增。感染后，Ifnar1(-/-) T 细胞表达高水平的自然细胞毒性触发受体 1 (NCR1) 配体，使其成为 NCR1 介导的 NK 细胞攻击的靶标。因此，T 细胞通过直接感知 I 型 IFNs 来保护自己免受 NK 细胞的杀伤，其机制是通过调节 NCR1 配体的表达，从而揭示了 T 细胞可以逃避 NK 细胞强大细胞毒性活性的一种机制。
