Mice lacking IL-12 develop polarized Th1 cells during viral infection.
Mice lacking IL-12 develop polarized Th1 cells during viral infection.
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DOI：
10.4049/jimmunol.160.8.3958
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发表时间：
1998-04
影响因子：
4.4
通讯作者：
V. Schijns;B. Haagmans;C. Wierda;Boudewijn P. T. Kruithof;I. Heijnen;G. Alber;M. Horzinek
中科院分区：
文献类型：
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作者：
V. Schijns;B. Haagmans;C. Wierda;Boudewijn P. T. Kruithof;I. Heijnen;G. Alber;M. Horzinek
在IL-12缺陷小鼠中的研究确定了IL-12产生Th 1细胞因子应答的必要性，这通常是消除细胞内病原体所需的。在这项研究中，我们证明了IL-12 p40和/或p35基因的靶向破坏小鼠有效地控制小鼠肝炎病毒（MHV）感染引起的肝损伤，类似于野生型动物。相反，MHV感染的IFN-γ受体缺陷（IFN-γ R [-/-]）小鼠对冠状病毒性肝炎的易感性增加。令人惊讶的是，缺乏IL-12的MHV感染小鼠产生了极化的Th 1型细胞因子应答，如由CD 4+脾细胞产生的高IFN-γ和不可检测的IL-4以及正常的病毒特异性血清IgG 2a/IgG 1比率所证明的。病毒诱导的1型细胞因子分泌模式在IL-12缺陷小鼠中通过体内中和IFN-γ或在接受IL-12中和Ab的IFN-γ R（-/-）小鼠中未逆转。在IL-12缺陷型小鼠中，用灭活的MHV免疫后也产生Th 1型应答。相比之下，用钥孔血蓝蛋白免疫后，缺乏IL-12的小鼠安装强烈降低特异性IgG 2a和增加IgE应答，指示2型主导的细胞因子模式。这些发现表明，病毒感染后，IL-12不是产生极化T细胞1型细胞因子表达和相关免疫应答所必需的，这与非病毒系统形成鲜明对比。我们的数据表明，即使在没有IL-12的情况下，病毒也可以选择性地诱导IFN-γ产生和Th 1型免疫反应。
Studies in IL-12-deficient mice established the necessity for IL-12 to generate a Th1 cytokine response that is often required for elimination of intracellular pathogens. In this study, we demonstrate that mice with a targeted disruption of the IL-12p40 and/or p35 gene effectively control liver damage induced by mouse hepatitis virus (MHV) infection, similar to wild-type animals. In contrast, MHV-infected IFN-gamma receptor-deficient (IFN-gammaR[-/-]) mice showed an increased susceptibility to coronaviral hepatitis. Surprisingly, MHV-infected mice lacking IL-12 produced a polarized Th1-type cytokine response, as evidenced by high IFN-gamma and nondetectable IL-4 production by CD4+ splenocytes and normal virus-specific serum IgG2a/IgG1 ratios. The virus-induced type 1 cytokine secretion pattern was not reversed in IL-12-deficient mice by in vivo neutralization of IFN-gamma nor in IFN-gammaR(-/-) mice receiving IL-12-neutralizing Abs. In IL-12-deficient mice, Th1-type responses were also generated upon immunization with inactivated MHV. In contrast, following immunization with keyhole limpet hemocyanin, mice lacking IL-12 mounted strongly reduced specific IgG2a and increased IgE responses, indicative of a type 2-dominated cytokine pattern. These findings demonstrate that following a virus infection, IL-12 is not essential for the generation of polarized T cell type 1 cytokine expression and associated immune responses, which is in marked contrast to nonviral systems. Our data suggest that viruses may selectively induce IFN-gamma production and Th1-type immune reactions even in the absence of IL-12.