Gas Plasma Technology Augments Ovalbumin Immunogenicity and OT-II T Cell Activation Conferring Tumor Protection in Mice.

Gas Plasma Technology Augments Ovalbumin Immunogenicity and OT-II T Cell Activation Conferring Tumor Protection in Mice.
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DOI:
10.1002/advs.202003395
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发表时间:
2021-05
期刊:
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
影响因子:
--
通讯作者:
Bekeschus S
Bekeschus S
中科院分区:
其他
文献类型:
--
作者:
Clemen R;Freund E;Mrochen D;Miebach L;Schmidt A;Rauch BH;Lackmann JW;Martens U;Wende K;Lalk M;Delcea M;Bröker BM;Bekeschus S

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活性氧(ROS/RNS)在炎症过程中产生,并引起蛋白质修饰,但免疫学后果在很大程度上是未知的。气体等离子体技术能够产生一个无与伦比的各种ROS/RNS部署模拟炎症和研究ROS/RNS修改的意义,使用模型蛋白鸡卵清蛋白(Ova与oxOva)。动态光散射和圆二色性光谱显示,在oxOva的结构修改相比,Ova。来自Ova特异性OT-II而不是来自C57 BL/6或SKH-1野生型小鼠的T细胞在Ova添加后呈现增强的活化。当离体或体内给药时,OxOva会加剧这种激活,沿着干扰素-γ产生增加,这是一种已知的抗黑色素瘤药物。野生型小鼠接种OxOva后接种同基因B16 F10表达Ova的黑色素瘤细胞,与接种Ova的小鼠相比,T细胞数量和活化增强,肿瘤负荷降低,抗原呈递细胞数量增加。使用质谱分析oxOva鉴定了三个富含与增加的T细胞活化相关的氧化修饰的热点区域。使用Ova作为模型蛋白,研究结果表明多ROS/RNS修饰的免疫调节作用可能会刺激炎症研究和肿瘤学疫苗接种策略的新研究路线。成功的疫苗接种需要增加抗原的免疫原性。冷物理等离子体产生能够引发氧化蛋白质修饰的活性氧和氮物质。卵清蛋白(Ova)的氧化显示T细胞活化增强,抗原呈递细胞数量增加,并在接种后降低体内肿瘤负荷。
Reactive oxygen species (ROS/RNS) are produced during inflammation and elicit protein modifications, but the immunological consequences are largely unknown. Gas plasma technology capable of generating an unmatched variety of ROS/RNS is deployed to mimic inflammation and study the significance of ROS/RNS modifications using the model protein chicken ovalbumin (Ova vs oxOva). Dynamic light scattering and circular dichroism spectroscopy reveal structural modifications in oxOva compared to Ova. T cells from Ova‐specific OT‐II but not from C57BL/6 or SKH‐1 wild type mice presents enhanced activation after Ova addition. OxOva exacerbates this activation when administered ex vivo or in vivo, along with an increased interferon‐gamma production, a known anti‐melanoma agent. OxOva vaccination of wild type mice followed by inoculation of syngeneic B16F10 Ova‐expressing melanoma cells shows enhanced T cell number and activation, decreased tumor burden, and elevated numbers of antigen‐presenting cells when compared to their Ova‐vaccinated counterparts. Analysis of oxOva using mass spectrometry identifies three hot spots regions rich in oxidative modifications that are associated with the increased T cell activation. Using Ova as a model protein, the findings suggest an immunomodulating role of multi‐ROS/RNS modifications that may spur novel research lines in inflammation research and for vaccination strategies in oncology. Successful vaccination requires increased immunogenicity of antigens. Cold physical plasmas produce reactive oxygen and nitrogen species capable of eliciting oxidative protein modifications. Oxidation of ovalbumin (Ova) shows enhanced T cell activation, elevated numbers of antigen‐presenting cells, and decreases tumor burden in vivo upon vaccination.
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