Institut National de la Santé et de la Recherche Médicale, Unit 970, Paris Cardiovascular Research Center, Paris, France.
Arterioscler Thromb Vasc Biol. 2012 Mar;32(3):605-12. doi: 10.1161/ATVBAHA.111.242800. Epub 2012 Jan 5.
The immunoinflammatory response plays a critical role in the development and progression of atherosclerosis. Recent studies suggested an important role for regulatory T (Treg) cells in the inhibition of disease-related vascular inflammation. We hypothesized that induction of a specific Treg cell response to atherosclerosis-relevant antigens would be an attractive strategy to limit the development and progression of atherosclerosis through the promotion of immune tolerance.
Young or old Apoe-/- mice were subcutaneously infused for 2 weeks with either a control ovalbumin (OVA) peptide or with apolipoprotein B100 (ApoB100)-derived peptides without adjuvant. Atherosclerosis development, progression and immunologic status were assessed at 8 weeks after the end of the infusion. Treatment with ApoB100 peptides led to significant reduction of lesion development in young Apoe-/- mice (P=0.001 versus OVA group) and abrogated atherosclerosis progression in old Apoe-/- mice with already established lesions (0% progression in ApoB100 versus 17% in OVA group, P<0.005). Limitation of plaque progression was associated with reduced vascular inflammation and increased collagen content, indicative of plaque stabilization. Infusion of ApoB100 peptides did not alterantibody production but promoted a specific Treg cell response, which was associated with a reduction of both T helper type 1-related and T helper type 2-related cytokines. Interestingly, depletion of CD4+CD25+ Treg cells abrogated ApoB100 peptides-dependent immune modulation and atheroprotection.
Subcutaneous infusion of adjuvant-free ApoB100-derived peptides to Apoe-/- mice reduces atherosclerosis through the induction of a specific Treg cell response.
免疫炎症反应在动脉粥样硬化的发生和发展中起着关键作用。最近的研究表明，调节性 T（Treg）细胞在抑制与疾病相关的血管炎症方面具有重要作用。我们假设，诱导针对动脉粥样硬化相关抗原的特异性 Treg 细胞反应将是一种有吸引力的策略，通过促进免疫耐受来限制动脉粥样硬化的发展和进展。
年轻或年老的 Apoe-/- 小鼠皮下注射 2 周对照卵清蛋白（OVA）肽或载脂蛋白 B100（ApoB100）衍生肽，无佐剂。在输注结束后 8 周评估动脉粥样硬化的发展、进展和免疫状态。用 ApoB100 肽治疗可显著减少年轻 Apoe-/- 小鼠的病变发展（P=0.001 与 OVA 组相比），并阻止已有病变的老年 Apoe-/- 小鼠的动脉粥样硬化进展（ApoB100 组无进展，而 OVA 组为 17%，P<0.005）。斑块进展的限制与血管炎症减少和胶原含量增加相关，表明斑块稳定。ApoB100 肽的输注不改变抗体产生，但促进了特异性 Treg 细胞反应，与 T 辅助 1 相关和 T 辅助 2 相关细胞因子的减少相关。有趣的是，CD4+CD25+Treg 细胞耗竭消除了 ApoB100 肽依赖的免疫调节和动脉粥样硬化保护作用。
将无佐剂的 ApoB100 衍生肽皮下注射到 Apoe-/- 小鼠中，通过诱导特异性 Treg 细胞反应来减少动脉粥样硬化。
