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载脂蛋白 B100 衍生肽在小鼠中引发的免疫应答。

Immune responses elicited by apoB-100-derived peptides in mice.

机构信息

Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, England, UK.

出版信息

Immunol Res. 2013 May;56(1):96-108. doi: 10.1007/s12026-013-8383-1.

Abstract

Peptides derived from apolipoprotein B (apoB)-100 have been previously used in vaccine preparations to treat atherosclerosis. Such vaccines have been shown to reduce atherosclerotic plaque development by 50 % in experimental animals, and this effect is associated with induction of T helper (Th)2 immune responses. In this study we immunised apolipoprotein E-deficient (apoE(-/-)) mice with apoB-100-derived peptides P2, P45 and P210. Animals received BSA-conjugated peptides or peptide-loaded bone marrow-derived dendritic cells (DCs). We used enzyme-linked immunosorbent assays to assess the synthesis of anti-peptide-specific IgG1 and IgG2a as well as the levels of interleukin (IL-)10 and interferon gamma (IFN-γ) in plasma of immunised animals. We also measured the effect of immunisation on the number of spleen-derived CD4(+) and CD8(+) regulatory T cells (Tregs) in these animals. Peptide and peptide-loaded DC immunisation significantly increased the levels of peptide-specific immunoglobulins and the number of Tregs in apoE(-/-) mice. This was accompanied by a significant increase in the secretion of IL-10 with no effect on IFN-γ levels. The results also show that the peptides can modulate the homing properties of DCs. Altogether, this study provides novel evidence for the immune mechanisms excerpted by apoB-100-derived peptides and their effect on Tregs and DCs relevant to their use in vaccine preparations.

摘要

载脂蛋白 B (apoB)-100 衍生肽先前已被用于疫苗制备以治疗动脉粥样硬化。此类疫苗已被证明可使实验动物的动脉粥样硬化斑块发展减少 50%,其作用与诱导 T 辅助(Th)2 免疫反应有关。在这项研究中,我们用 apoB-100 衍生肽 P2、P45 和 P210 免疫载脂蛋白 E 缺陷(apoE(-/-))小鼠。动物接受 BSA 缀合肽或负载肽的骨髓来源树突状细胞(DC)。我们使用酶联免疫吸附测定法来评估免疫动物血浆中抗肽特异性 IgG1 和 IgG2a 的合成以及白细胞介素(IL)-10 和干扰素γ(IFN-γ)的水平。我们还测量了免疫对这些动物脾脏来源的 CD4(+)和 CD8(+)调节性 T 细胞(Tregs)数量的影响。肽和负载肽的 DC 免疫显著增加了 apoE(-/-)小鼠中肽特异性免疫球蛋白和 Tregs 的数量。这伴随着 IL-10 分泌的显著增加,而对 IFN-γ 水平没有影响。结果还表明,这些肽可以调节 DC 的归巢特性。总之,这项研究为 apoB-100 衍生肽的免疫机制及其对 Tregs 和 DC 的影响提供了新的证据,这些机制与它们在疫苗制备中的应用有关。

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