PDF(Pubmed)
Abstract：
UNASSIGNED: Modified Vaccinia Virus Ankara (MVA) is a safe vaccine vector inducing long- lasting and potent immune responses. MVA-mediated CD8+T cell responses are optimally induced, if both, direct- and cross-presentation of viral or recombinant antigens by dendritic cells are contributing.
UNASSIGNED: To improve the adaptive immune responses, we investigated the role of the purinergic receptor P2X7 (P2RX7) in MVA-infected feeder cells as a modulator of cross-presentation by non-infected dendritic cells. The infected feeder cells serve as source of antigen and provide signals that help to attract dendritic cells for antigen take up and to license these cells for cross-presentation.
UNASSIGNED: We demonstrate that presence of an active P2RX7 in major histocompatibility complex (MHC) class I (MHCI) mismatched feeder cells significantly enhanced MVA-mediated antigen cross-presentation. This was partly regulated by P2RX7-specific processes, such as the increased availability of extracellular particles as well as the altered cellular energy metabolism by mitochondria in the feeder cells. Furthermore, functional P2RX7 in feeder cells resulted in a delayed but also prolonged antigen expression after infection.
UNASSIGNED: We conclude that a combination of the above mentioned P2RX7-depending processes leads to significantly increased T cell activation via cross- presentation of MVA-derived antigens. To this day, P2RX7 has been mostly investigated in regards to neuroinflammatory diseases and cancer progression. However, we report for the first time the crucial role of P2RX7 for antigen- specific T cell immunity in a viral infection model.
UNASSIGNED: To improve the adaptive immune responses, we investigated the role of the purinergic receptor P2X7 (P2RX7) in MVA-infected feeder cells as a modulator of cross-presentation by non-infected dendritic cells. The infected feeder cells serve as source of antigen and provide signals that help to attract dendritic cells for antigen take up and to license these cells for cross-presentation.
UNASSIGNED: We demonstrate that presence of an active P2RX7 in major histocompatibility complex (MHC) class I (MHCI) mismatched feeder cells significantly enhanced MVA-mediated antigen cross-presentation. This was partly regulated by P2RX7-specific processes, such as the increased availability of extracellular particles as well as the altered cellular energy metabolism by mitochondria in the feeder cells. Furthermore, functional P2RX7 in feeder cells resulted in a delayed but also prolonged antigen expression after infection.
UNASSIGNED: We conclude that a combination of the above mentioned P2RX7-depending processes leads to significantly increased T cell activation via cross- presentation of MVA-derived antigens. To this day, P2RX7 has been mostly investigated in regards to neuroinflammatory diseases and cancer progression. However, we report for the first time the crucial role of P2RX7 for antigen- specific T cell immunity in a viral infection model.
摘要：
修饰的安卡拉痘苗病毒(MVA)是诱导持久和有效的免疫应答的安全疫苗载体。MVA介导的CD8+T细胞反应最佳诱导，如果两者兼而有之,通过树突细胞直接和交叉呈递病毒或重组抗原是有贡献的。
■为了改善适应性免疫反应，我们研究了嘌呤能受体P2X7(P2RX7)在MVA感染的饲养细胞中作为未感染树突状细胞交叉呈递调节剂的作用.受感染的饲养细胞充当抗原的来源,并提供有助于吸引树突细胞用于抗原摄取并许可这些细胞用于交叉呈递的信号。
我们证明了在主要组织相容性复合体(MHC)I类(MHCI)错配饲养细胞中存在活性P2RX7显著增强了MVA介导的抗原交叉呈递。这部分受到P2RX7特定过程的调节，例如细胞外颗粒的可用性增加以及饲养细胞中线粒体的细胞能量代谢改变。此外，饲养细胞中的功能性P2RX7导致感染后抗原表达延迟但也延长。
我们得出结论,上述P2RX7依赖性过程的组合通过MVA衍生抗原的交叉呈递导致显著增加的T细胞活化。直到今天,P2RX7主要针对神经炎症性疾病和癌症进展进行研究。然而,我们首次报道了P2RX7在病毒感染模型中对抗原特异性T细胞免疫的重要作用。
■为了改善适应性免疫反应，我们研究了嘌呤能受体P2X7(P2RX7)在MVA感染的饲养细胞中作为未感染树突状细胞交叉呈递调节剂的作用.受感染的饲养细胞充当抗原的来源,并提供有助于吸引树突细胞用于抗原摄取并许可这些细胞用于交叉呈递的信号。
我们证明了在主要组织相容性复合体(MHC)I类(MHCI)错配饲养细胞中存在活性P2RX7显著增强了MVA介导的抗原交叉呈递。这部分受到P2RX7特定过程的调节，例如细胞外颗粒的可用性增加以及饲养细胞中线粒体的细胞能量代谢改变。此外，饲养细胞中的功能性P2RX7导致感染后抗原表达延迟但也延长。
我们得出结论,上述P2RX7依赖性过程的组合通过MVA衍生抗原的交叉呈递导致显著增加的T细胞活化。直到今天,P2RX7主要针对神经炎症性疾病和癌症进展进行研究。然而,我们首次报道了P2RX7在病毒感染模型中对抗原特异性T细胞免疫的重要作用。
