Lucas Mathias, Schachterle William, Oberle Karin, Aichele Peter, Diefenbach Andreas
Skirball Institute of Biomolecular Medicine, Program in Molecular Pathogenesis, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.
Immunity. 2007 Apr;26(4):503-17. doi: 10.1016/j.immuni.2007.03.006. Epub 2007 Mar 29.
Natural killer (NK) cells are important effector cells in the control of infections. The cellular and molecular signals required for NK cell activation in vivo remain poorly defined. By using a mouse model for the inducible ablation of dendritic cells (DCs), we showed that the in vivo priming of NK cell responses to viral and bacterial pathogens required the presence of CD11c(high) DCs. After peripheral Toll-like receptor (TLR) stimulation, NK cells were recruited to local lymph nodes, and their interaction with DCs resulted in the emergence of effector NK cells in the periphery. NK cell priming was dependent on the recognition of type I IFN signals by DCs and the subsequent production and trans-presentation of IL-15 by DCs to resting NK cells. CD11c(high) DC-derived IL-15 was necessary and sufficient for the priming of NK cells. Our data define a unique in vivo role of DCs for the priming of NK cells, revealing a striking and previously unappreciated homology to T lymphocytes of the adaptive immune system.
自然杀伤（NK）细胞是控制感染过程中的重要效应细胞。体内NK细胞激活所需的细胞和分子信号仍不清楚。通过使用一种可诱导树突状细胞（DC）消融的小鼠模型，我们发现体内NK细胞对病毒和细菌病原体反应的启动需要CD11c（高）DC的存在。外周Toll样受体（TLR）刺激后，NK细胞被招募到局部淋巴结，它们与DC的相互作用导致外周效应NK细胞的出现。NK细胞的启动依赖于DC对I型干扰素信号的识别以及随后DC向静止NK细胞产生和反式呈递白细胞介素-15。CD11c（高）DC来源的白细胞介素-15对于NK细胞的启动是必要且充分的。我们的数据定义了DC在体内启动NK细胞的独特作用，揭示了与适应性免疫系统T淋巴细胞惊人且以前未被认识到的同源性。
