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

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Gas Plasma Technology Augments Ovalbumin Immunogenicity and OT-II T Cell Activation Conferring Tumor Protection in Mice
Advanced Science ( IF 14.3 ) Pub Date : 2021-03-08 , DOI: 10.1002/advs.202003395
Ramona Clemen ₁ , Eric Freund _{1,

2} , Daniel Mrochen _{1,

3} , Lea Miebach _{1,

2} , Anke Schmidt ₁ , Bernhard H Rauch ₄ , Jan-Wilm Lackmann ₅ , Ulrike Martens _{6,

7} , Kristian Wende ₁ , Michael Lalk ₇ , Mihaela Delcea _{6,

7} , Barbara M Bröker ₃ , Sander Bekeschus ₁

Affiliation

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.

中文翻译：

气体等离子体技术增强卵清蛋白免疫原性和 OT-II T 细胞激活，赋予小鼠肿瘤保护作用

活性氧 (ROS/RNS) 在炎症过程中产生并引发蛋白质修饰，但其免疫学后果很大程度上未知。气体等离子体技术能够产生无与伦比的各种 ROS/RNS，用于模拟炎症并使用模型蛋白鸡卵清蛋白（Ova 与 oxOva）研究 ROS/RNS 修饰的重要性。动态光散射和圆二色光谱揭示了 oxOva 与 Ova 相比的结构变化。来自 Ova 特异性 OT-II 而非 C57BL/6 或 SKH-1 野生型小鼠的 T 细胞在添加 Ova 后表现出增强的激活。当离体或体内施用时，OxOva 会加剧这种激活，同时增加干扰素-γ（一种已知的抗黑色素瘤药物）的产生。与接种 Ova 的小鼠相比，对野生型小鼠进行 OxOva 疫苗接种，然后接种同源 B16F10 Ova 表达黑色素瘤细胞，结果显示 T 细胞数量和活化增强，肿瘤负荷减少，抗原呈递细胞数量增加。使用质谱分析 oxOva 确定了三个富含氧化修饰的热点区域，这些氧化修饰与 T 细胞激活增加相关。使用 Ova 作为模型蛋白，研究结果表明多 ROS/RNS 修饰具有免疫调节作用，可能会刺激炎症研究和肿瘤学疫苗接种策略的新研究方向。

更新日期：2021-03-08

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