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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >A DNA adjuvant encoding a fusion protein between anti-CD3 single-chain Fv and AIMP1 enhances T helper type 1 cell-mediated immune responses in antigen-sensitized mice.
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A DNA adjuvant encoding a fusion protein between anti-CD3 single-chain Fv and AIMP1 enhances T helper type 1 cell-mediated immune responses in antigen-sensitized mice.

机译:编码抗CD3单链Fv与AIMP1之间融合蛋白的DNA佐剂可增强抗原敏感小鼠中T辅助1型细胞介导的免疫反应。

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摘要

T helper type 1 (Th1) cell-mediated immune responses contribute to host defences against intracellular pathogen infections and cancer. Previously, we found that aminoacyl tRNA synthetase-interacting multifunctional protein 1 (AIMP1) activated macrophages and dendritic cells to enhance Th1 responses. Herein, we manipulated this property to improve Th1 immune responses in vivo by constructing a mammalian expression plasmid (pAnti-CD3sFv/AIMP1) encoding AIMP1 fused to the anti-CD3 single-chain Fv (sFv), the smallest unit of the antibody that interacts with the CD3epsilon region of the T-cell receptor. Intramuscular injection of ovalbumin (OVA)-sensitized BALB/c mice with pAnti-CD3sFv/AIMP1 DNA adjuvant increased the OVA-specific, interferon-gamma production by their CD4(+) T cells and the levels of anti-OVA immunoglobulin G2a (IgG2a) isotype in their sera. Furthermore, the pAnti-CD3sFv/AIMP1 DNA adjuvant decreased interleukin-4 production and anti-OVA IgE levels in the OVA-injected mice. Importantly, the pAnti-CD3sFv/AIMP1 was more efficient than a mixture of pAnti-CD3sFv and pAIMP1 in inducing OVA-specific Th1 immune responses and also in inhibiting OVA-specific Th2 responses during antigen priming. These studies indicated that the pAnti-CD3sFv/AIMP1 fusion DNA adjuvant enhanced Th1 immune responses in antigen-sensitized mice.
机译:T辅助1型(Th1)细胞介导的免疫反应有助于宿主防御细胞内病原体感染和癌症。以前,我们发现,与氨酰tRNA合成酶相互作用的多功能蛋白1(AIMP1)激活巨噬细胞和树突状细胞以增强Th1反应。在本文中,我们通过构建编码AIMP1的哺乳动物表达质粒(pAnti-CD3sFv / AIMP1)来操纵该特性,以改善体内Th1免疫反应,该AIMP1与抗CD3单链Fv(sFv)融合,这是与抗体相互作用的最小单位T细胞受体的CD3ε区域。用pAnti-CD3sFv / AIMP1 DNA佐剂肌肉注射卵清蛋白(OVA)致敏的BALB / c小鼠可通过其CD4(+)T细胞和抗OVA免疫球蛋白G2a(IgG2a)的水平增加OVA特异性干扰素-γ的产生)的血清型。此外,pAnti-CD3sFv / AIMP1 DNA佐剂在注射OVA的小鼠中降低了白介素4的产生和抗OVA IgE的水平。重要的是,pAnti-CD3sFv / AIMP1比pAnti-CD3sFv和pAIMP1的混合物在诱导OVA特异性Th1免疫应答以及在抗原引发过程中抑制OVA特异性Th2应答的效率更高。这些研究表明,pAnti-CD3sFv / AIMP1融合DNA佐剂可增强抗原敏感小鼠的Th1免疫应答。

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