An absolute and restricted requirement for IL-12 in natural killer cell IFN-gamma production and antiviral defense. Studies of natural killer and T cell responses in contrasting viral infections.
An absolute and restricted requirement for IL-12 in natural killer cell IFN-gamma production and antiviral defense. Studies of natural killer and T cell responses in contrasting viral infections.
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DOI：
10.4049/jimmunol.156.3.1138
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发表时间：
1996-02
影响因子：
4.4
通讯作者：
J. Orange;C. Biron
中科院分区：
文献类型：
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作者：
J. Orange;C. Biron
IL-12是IFN-γ的有效诱导剂，并且与多种免疫调节活性相关。使用小鼠巨细胞病毒（MCMV）和淋巴细胞性脉络丛脑膜炎病毒（LCMV）的急性病毒感染模型，我们在这里表明，IL-12整体参与抗病毒免疫的某些方面。评价IL-12的产生和功能的实验证明，在Smith株MCMV感染的早期诱导生物活性因子，而不是Armstrong株LCMV感染。MCMV诱导的IL-12负责早期NK细胞IFN-γ产生和病毒控制，因为通过Ab处理的体内IL-12中和阻断了这两者。与此相反，NK细胞IFN-γ的产生不能在LCMV感染期间检测到，IL-12中和对早期LCMV复制没有影响。在这两种感染中，中和IL-12的治疗未能改变早期NK细胞的细胞毒性或后期T细胞应答，包括感染后第7天和第9天的IFN-γ产生和病毒清除。这些数据证明了在某些病毒感染期间诱导IL-12产生以及IL-12用于引发NK细胞IFN-γ产生和抗病毒防御的功能。此外，它们表明存在IL-12非依赖性的IFN-γ诱导机制和T细胞的病毒控制。
IL-12 is a potent induce of IFN-gamma and is associated with a wide variety of immunoregulatory activities. Using murine CMV (MCMV) and lymphocytic choriomeningitis virus (LCMV) models of acute viral infection, we show here that IL-12 is integrally involved in certain aspects of antiviral immunity. Experiments evaluating the production and function of IL-12 demonstrated the induction of biologically active factor early during Smith strain MCMV, but not Armstrong strain LCMV, infection. The MCMV-induced IL-12 was responsible for early NK cell IFN-gamma production and viral control, as in vivo IL-12 neutralization by Ab treatment blocked both of these. In contrast, NK cell IFN-gamma production could not be detected during LCMV infection, and IL-12 neutralization had no effect on early LCMV replication. In both infections, treatments neutralizing IL-12 failed to alter either early NK cell cytotoxicity or later T cell responses, including IFN-gamma production and viral clearance on days 7 and 9 after infection. These data demonstrate the induction of IL-12 production during certain viral infections and the function of IL-12 for eliciting NK cell IFN-gamma production and antiviral defense. Furthermore, they suggest the existence of IL-12-independent mechanisms for IFN-gamma induction and viral control by T cells.