NK cell-like behavior of Valpha14i NK T cells during MCMV infection.
NK cell-like behavior of Valpha14i NK T cells during MCMV infection.
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MCMV感染过程中valpha14i NK T细胞的NK细胞样行为。
DOI：
10.1371/journal.ppat.1000106
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发表时间：
2008-07-18
期刊：
影响因子：
6.7
通讯作者：
Brossay, Laurent
中科院分区：
文献类型：
--
作者：
Wesley, Johnna D.;Tessmer, Marlowe S.;Chaukos, Deanna;Brossay, Laurent
对鼠巨细胞病毒 (MCMV) 的免疫很大程度上取决于病毒复制初始遏制、活动性感染消退以及抗病毒反应适应阶段的正确诱导的先天反应。与 NK 细胞相反，Vα14 不变自然杀伤 T 细胞对 MCMV 的反应尚未得到检验。我们发现，Vα14i NK T 细胞在 MCMV 感染后被激活并产生显着水平的 IFN-γ，但不会增殖或产生 IL-4。使用抗 CD1d mAb 进行体内治疗并将 Vα14i NK T 细胞过继转移至 MCMV 感染的 CD1d−/− 小鼠中，表明 CD1d 对于 Vα14i NK T 细胞激活是可有可无的。相反，IFN-α/β 和 IL-12 都是最佳激活所必需的。 Vα14i NK T 细胞衍生的 IFN-γ 部分依赖于 IFN-α/β，但高度依赖于 IL-12。 Vα14i NK T 细胞有助于对 MCMV 的免疫反应并放大 NK 细胞衍生的 IFN-γ。重要的是，与杂合子同窝对照相比，CD1d−/− 小鼠对高剂量 MCMV 感染的死亡率增加。总的来说，这些发现说明了 Vα14i NK T 细胞的可塑性，它们在细菌感染期间充当效应 T 细胞，但在针对 MCMV 感染的先天免疫反应期间具有类似 NK 细胞的行为。对病毒感染的有效免疫反应需要先天性免疫细胞和适应性免疫细胞。自然杀伤 (NK) 细胞是针对鼠巨细胞病毒 (MCMV) 的免疫反应的关键先天细胞成分。自然杀伤 T (NK T) 细胞是非经典 T 细胞，有潜力桥接免疫系统的两个分支。然而，NK T 细胞对抗病毒免疫反应的贡献尚未得到广泛研究。在没有额外刺激的情况下，NK T 细胞积极参与针对 MCMV 感染的免疫反应。有趣的是，与它们对细菌的反应相反，我们证明在病毒感染期间只有先天性 NK T 细胞臂被激活，而适应性分支（CD1d 与 TCR 的结合）是可有可无的。 NK T 细胞显示出响应病毒感染的激活迹象、CD25 表达增加、细胞数量迅速减少以及抗病毒细胞因子 IFN-γ 的产生。 NK T 细胞对 MCMV 的反应也会影响 NK 细胞活性和炎症细胞因子谱。了解这些独特 T 细胞在感染情况下的生理功能将有助于开发针对病毒感染的新型治疗和预防疗法。
Immunity to the murine cytomegalovirus (MCMV) is critically dependent on the innate response for initial containment of viral replication, resolution of active infection, and proper induction of the adaptive phase of the anti-viral response. In contrast to NK cells, the Vα14 invariant natural killer T cell response to MCMV has not been examined. We found that Vα14i NK T cells become activated and produce significant levels of IFN-γ, but do not proliferate or produce IL-4 following MCMV infection. In vivo treatment with an anti-CD1d mAb and adoptive transfer of Vα14i NK T cells into MCMV-infected CD1d−/− mice demonstrate that CD1d is dispensable for Vα14i NK T cell activation. In contrast, both IFN-α/β and IL-12 are required for optimal activation. Vα14i NK T cell–derived IFN-γ is partially dependent on IFN-α/β but highly dependent on IL-12. Vα14i NK T cells contribute to the immune response to MCMV and amplify NK cell–derived IFN-γ. Importantly, mortality is increased in CD1d−/− mice in response to high dose MCMV infection when compared to heterozygote littermate controls. Collectively, these findings illustrate the plasticity of Vα14i NK T cells that act as effector T cells during bacterial infection, but have NK cell–like behavior during the innate immune response to MCMV infection. An efficient immune response to viral infection requires both innate and adaptive immune cells. Natural killer (NK) cells are a critical innate cellular component of the immune response to murine cytomegalovirus (MCMV). Natural killer T (NK T) cells are non-classical T cells that have the potential to bridge the two arms of the immune system. However, the contribution of NK T cells to the anti-viral immune response has not been extensively studied. In the absence of additional stimuli, NK T cells actively participate in the immune response to MCMV infection. Interestingly, in contrast to their response to bacteria, we demonstrate that only the innate NK T cell arm is activated during viral infection while the adaptive branch, TCR engagement by CD1d, is dispensable. NK T cells display signs of activation in response to viral infection, increased expression of CD25, a rapid decrease in cell number, and production of the anti-viral cytokine IFN-γ. The NK T cell response to MCMV also influences the NK cell activity and the inflammatory cytokine profiles. Understanding the physiological function of these unique T cells in the context of infection will aid in the development of novel therapeutic and preventive treatments for viral infections.
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