Overexpression of Interleukin-15 Increases Susceptibility to Lipopolysaccharide-Induced Liver Injury in Mice Primed with Mycobacterium bovis Bacillus Calmette-Guérin

Overexpression of Interleukin-15 Increases Susceptibility to Lipopolysaccharide-Induced Liver Injury in Mice Primed with Mycobacterium bovis Bacillus Calmette-Guérin
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DOI：
10.1128/iai.72.7.3855-3862.2004
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发表时间：
2004-07
期刊：
Infection and Immunity
影响因子：
3.1
通讯作者：
T. Yajima;H. Nishimura;Kimika Saito;H. Kuwano;Y. Yoshikai
T. Yajima;H. Nishimura;Kimika Saito;H. Kuwano;Y. Yoshikai
中科院分区：
医学2区
文献类型：
--
作者：
T. Yajima;H. Nishimura;Kimika Saito;H. Kuwano;Y. Yoshikai

文献摘要

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摘要 用牛分枝杆菌卡介苗 (BCG) 引发的小鼠对脂多糖 (LPS) 诱导的肝损伤和致死高度敏感。我们发现，用 BCG 引发的白细胞介素 15 (IL-15) 转基因 (Tg) 小鼠比非 Tg 小鼠更容易受到 LPS 诱导的肝损伤。注射 LPS 后，BCG 引发的 IL-15 Tg 小鼠肝脏中表达细胞内 γ 干扰素 (IFN-γ) 的 CD44+ CD8+ T 细胞数量显着增加，并且 BCG 引发的 IL-15 Tg 小鼠中 CD8+ T 细胞的耗竭完全消除了对 LPS 诱导致死的敏感性。来自 BCG 引发的 IL-15 Tg 小鼠的肝脏 T 细胞在体外响应 LPS 产生 IFN-γ，而添加抗 IL-12 单克隆抗体 (MAb) 可抑制该现象。注射 LPS 后，用抗 IL-12 MAb 体内治疗可抑制表达胞内 IFN-γ 的 CD44+ CD8+ T 细胞的出现。这些结果表明，IL-15 的过度表达通过 CD8+ T 细胞的旁观者激活，增加了 BCG 引发的小鼠对 LPS 诱导的肝损伤的易感性。
ABSTRACT Mice primed with Mycobacterium bovis bacillus Calmette-Guérin (BCG) are highly sensitive to lipopolysaccharide (LPS)-induced liver injury and lethality. We found that interleukin-15 (IL-15) transgenic (Tg) mice primed with BCG were more susceptible to LPS-induced liver injury than non-Tg mice. The numbers of CD44+ CD8+ T cells expressing intracellular gamma interferon (IFN-γ) significantly increased in the livers of BCG-primed IL-15 Tg mice after LPS injection, and the depletion of CD8+ T cells from BCG-primed IL-15 Tg mice completely abolished the susceptibility to LPS-induced lethality. Liver T cells from BCG-primed IL-15 Tg mice produced IFN-γ in vitro in response to LPS, which was inhibited by the addition of anti-IL-12 monoclonal antibody (MAb). In vivo treatment with anti-IL-12 MAb inhibited the appearance of CD44+ CD8+ T cells expressing intracellular IFN-γ after LPS injection. These results suggest that the overexpression of IL-15 increases susceptibility to LPS-induced liver injury in BCG-primed mice via bystander activation of CD8+ T cells.