Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
J Exp Med. 2012 May 7;209(5):947-54. doi: 10.1084/jem.20111760. Epub 2012 Apr 9.
Although natural killer (NK) cells are classified as innate immune cells, recent studies demonstrate that NK cells can become long-lived memory cells and contribute to secondary immune responses. The precise signals that promote generation of long-lived memory NK cells are unknown. Using cytokine receptor-deficient mice, we show that interleukin-12 (IL-12) is indispensible for mouse cytomegalovirus (MCMV)-specific NK cell expansion and generation of memory NK cells. In contrast to wild-type NK cells that proliferated robustly and resided in lymphoid and nonlymphoid tissues for months after MCMV infection, IL-12 receptor-deficient NK cells failed to expand and were unable to mediate protection after MCMV challenge. We further demonstrate that a STAT4-dependent IFN-γ-independent mechanism contributes toward the generation of memory NK cells during MCMV infection. Understanding the full contribution of inflammatory cytokine signaling to the NK cell response against viral infection will be of interest for the development of vaccines and therapeutics.
虽然自然杀伤 (NK) 细胞被归类为先天免疫细胞，但最近的研究表明，NK 细胞可以成为长寿记忆细胞，并有助于二次免疫反应。促进长寿记忆 NK 细胞产生的确切信号尚不清楚。使用细胞因子受体缺陷型小鼠，我们表明白细胞介素-12 (IL-12) 对于小鼠巨细胞病毒 (MCMV) 特异性 NK 细胞扩增和记忆 NK 细胞的产生是必不可少的。与在 MCMV 感染后数月内在淋巴和非淋巴组织中大量增殖并存在的野生型 NK 细胞不同，IL-12 受体缺陷型 NK 细胞未能扩增，并且在 MCMV 攻击后无法介导保护。我们进一步表明，STAT4 依赖性 IFN-γ 非依赖性机制有助于在 MCMV 感染期间产生记忆 NK 细胞。了解炎症细胞因子信号对 NK 细胞对抗病毒感染反应的全面贡献，对于疫苗和治疗药物的开发将具有重要意义。
