IL-18, but not IL-12, is required for optimal cytokine production by influenza virus-specific CD8+ T cells
IL-18, but not IL-12, is required for optimal cytokine production by influenza virus-specific CD8+ T cells
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DOI：
10.1002/eji.200636766
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发表时间：
2007-02-01
影响因子：
5.4
通讯作者：
La Gruta, Nicole L.
中科院分区：
文献类型：
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作者：
Denton, Alice E.;Doherty, Peter C.;La Gruta, Nicole L.
有效的先天性细胞因子IL-12和IL-18被认为是NK细胞和T淋巴细胞产生IFN-γ的重要抗原非依赖性介质。本分析阐述了IL-12和IL-18在病毒特异性CD 8（+）T细胞产生中的生理作用。用甲型流感病毒感染wt C57 BL/6 J（B6）小鼠和IL-12 p40（IL-12 p40（-/-））或IL-18（IL-18（-/-））基因被破坏的小鼠，并比较所得表位特异性CD 8（+）T细胞应答的特征。虽然IL-12似乎对病毒生长或CD 8（+）T细胞应答谱没有显著影响，但IL-18的缺乏与肺中病毒清除延迟有关，尽管数量正常，但表位特异性CD 8（+）T细胞产生的IFN-γ、TNF-α和IL-2显著减少。虽然这种细胞因子表型在IL-12 p40/IL-18双敲除小鼠中广泛维持，但没有观察到任何累加效应的证据。总之，我们的研究结果表明，IL-18，而不是IL-12，诱导CD 8（+）T细胞的关键细胞因子的最佳，抗原特异性生产的流感病毒从感染小鼠的肺部有效清除。
The potent innate cytokines IL-12 and IL-18 are considered to be important antigen-independent mediators of IFN-gamma production by NK cells and T lymphocytes. The present analysis addresses the physiological role of IL-12 and IL-18 in the generation of virus-specific CD8(+) T cells. Both wt C57BL/6J (B6) mice and mice with disrupted IL-12p40 (IL-12p40(-/-)) or IL-18 (IL-18(-/-)) genes were infected with an influenza A virus and the characteristics of the resultant epitope-specific CD8(+) T cell responses were compared. While IL-12 appeared to have no notable effect on either virus growth or on CD8(+) T cell response profiles, the absence of IL-18 was associated with delayed virus clearance from the lung and, despite normal numbers, a significantly reduced production of IFN-gamma, TNF-alpha, and IL-2 by epitope-specific CD8(+) T cells. While this cytokine phenotype was broadly maintained in IL-12p40/IL-18 double-knockout mice, no evidence was seen for any additive effect. Together, our results suggest that IL-18, but not IL-12, induces optimal, antigen-specific production of key cytokines by CD8(+) T cells for the efficient clearance of influenza virus from the lungs of infected mice.