Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, The Netherlands.
J Leukoc Biol. 2012 Sep;92(3):605-10. doi: 10.1189/jlb.0112045. Epub 2012 Jun 13.
Viral recognition programs DCs to express Signal 3 molecules that promote the differentiation of effector CD8(+) T cells. Besides IL-12, another DC-derived IL-12 family member, IL-27, has been reported to contribute herein, but its specific role is not well understood. Here, we show that whereas IL-12 potently induces inflammatory cytokines (i.e., IFN-γ and TNF-α, but not IL-2), IL-27 excels in inducing proliferation and a cytotoxic profile (GrB, cytotoxicity of target cells) in human naïve CD8(+) T cells. Compared with bacterial cell-wall peptidoglycan, viral dsRNA-mimic poly (I:C) is superior in priming human BDCA1(+) peripheral blood DCs to produce IL-12 and IL-27, which promote inflammatory cytokines and a cytotoxic profile in differentiating CD8(+) T cells, respectively. These data support the concept that viral dsRNA-activated human DCs produce IL-27 to act as a specialized procytotoxic, antiviral cytokine in the development of effector CD8(+) T cells.
病毒识别程序可诱导 DC 表达信号 3 分子，促进效应性 CD8(+)T 细胞的分化。除了 IL-12 以外，另一种 DC 衍生的 IL-12 家族成员 IL-27 也被报道在此过程中发挥作用，但它的具体作用尚不清楚。在这里，我们发现，IL-12 可强烈诱导炎症细胞因子（即 IFN-γ和 TNF-α，但不诱导 IL-2），而 IL-27 则擅长诱导人幼稚 CD8(+)T 细胞的增殖和细胞毒性特征（GrB，靶细胞的细胞毒性）。与细菌细胞壁肽聚糖相比，病毒双链 RNA 模拟物聚（I：C）在刺激人外周血 BDCA1(+)DC 产生 IL-12 和 IL-27 方面更为优越，分别促进分化 CD8(+)T 细胞中炎症细胞因子和细胞毒性特征的产生。这些数据支持这样的概念，即病毒双链 RNA 激活的人 DC 产生 IL-27，作为效应性 CD8(+)T 细胞发育中的一种特殊的促细胞毒性、抗病毒细胞因子。
