Natural killer cell responses to dendritic cells infected by the ANRS HIV-1 vaccine candidate, MVAHIV
Natural killer cell responses to dendritic cells infected by the ANRS HIV-1 vaccine candidate, MVAHIV
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DOI：
10.1016/j.vaccine.2014.07.094
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发表时间：
2014-09-29
期刊：
影响因子：
5.5
通讯作者：
Scott-Algara, Daniel
中科院分区：
文献类型：
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作者：
Cummings, Jean-Saville;Moreno-Nieves, Uriel Y.;Scott-Algara, Daniel
先天机制对于宿主对抗原的免疫反应的发展至关重要。特别是，自然杀伤（NK）细胞和树突状细胞（DC）之间的早期相互作用极大地影响先天性和适应性免疫反应的建立。在这项研究中，我们使用自体体外共培养系统分析了 NK 细胞对 MVA(HIV) 感染的 DC 的反应，以及这些 MVA(HIV) 引发的 NK 细胞随后控制自体 DC 中 HIV-1 感染的能力。我们发现 NK 细胞在脱颗粒和细胞因子产生方面对 MVA(HIV) 或 MVA(WT) 感染的 DC 做出早期反应。经过 MVA(HIV) 或 MVA(WT) 感染的 DC 对 NK 细胞进行 4 天引发后，我们观察到 NK 细胞受体库表达的增殖和调节增强。有趣的是，我们发现与 MVA(WT) 引发的 NK 细胞相比，MVA(HIV) 引发的 NK 细胞在自体 DC 中控制 HIV-1 感染的能力显着更高。这种增强的抗 HIV-1 活性似乎是 HIV 特异性的，因为 MVA(HIV) 引发的 NK 细胞没有更好的能力控制其他病毒感染或对肿瘤细胞做出反应。此外，我们观察到 NK 细胞受体 NKG2D 和 NKp46 调节 NK 细胞的启动。该数据提供证据表明，在 NK/DC 培养物中，体外 NK 细胞可以由病毒载体感染的 DC 引发，以特异性靶向病毒感染的细胞。 (C) 2014 Elsevier Ltd. 保留所有权利。
Innate mechanisms are critical for the development of the host immune responses to antigen. Particularly, early interaction between natural killer (NK) cells and dendritic cells (DC) greatly impacts the establishment of both innate and adaptive immune responses. In this study, using an autologous in vitro co-culture system we analyzed the NK cell response against MVA(HIV)-infected DC as well as the subsequent ability of these MVA(HIV)-primed NK cells to control HIV-1 infection in autologous DC. We found that NK cells responded early to MVA(HIV)- or MVA(WT)-infected DC in terms of degranulation and cytokine production. After a 4-day priming of NK cells by MVA(HIV)- or MVA(WT)-infected DC we observed an enhanced proliferation and modulation in the NK cell receptor repertoire expression. Interestingly, we found that MVA(HIV)-primed NK cells had a significant higher ability to control HIV-1 infection in autologous DC compared to MVA(WT)-primed NK cells; and this enhanced anti-HIV-1 activity appeared to be HIV-specific as MVA(HIV)-primed NK cells did not have a better ability to control other viral infections or respond against tumoral cells. Furthermore, we observed that NK cell receptors NKG2D and NKp46 modulate the priming of NK cells. This data provides evidence that in vitro NK cells can be primed by viral vector-infected DC, in the context of a NK/DC culture, to specifically target viral infected cells. (C) 2014 Elsevier Ltd. All rights reserved.