CD3 antibody and IL-2 complex combination therapy inhibits atherosclerosis by augmenting a regulatory immune response.
CD3 antibody and IL-2 complex combination therapy inhibits atherosclerosis by augmenting a regulatory immune response.
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DOI：
10.1161/jaha.113.000719
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发表时间：
2014-04-22
影响因子：
5.4
通讯作者：
Hirata K
中科院分区：
文献类型：
--
作者：
Kasahara K;Sasaki N;Yamashita T;Kita T;Yodoi K;Sasaki Y;Takeda M;Hirata K
越来越多的证据表明，致病性效应T细胞（Teffs）和调节性T细胞（Tregs）之间的平衡可能对控制动脉粥样硬化疾病很重要。我们假设抗CD3抗体（CD3‐Ab）和IL‐2/抗IL‐2单克隆抗体复合物（IL‐2复合物）联合治疗旨在增加Tregs与Teffs的比例，可以有效抑制小鼠动脉粥样硬化。我们用载脂蛋白E缺乏小鼠喂食高胆固醇饮食，用载脂蛋白、CD3‐Ab、IL‐2复合物或它们的组合治疗。与单独使用CD3‐Ab或IL‐2复合物治疗的小鼠相比，接受联合治疗的小鼠动脉粥样硬化病变明显减少。此外，观察到淋巴器官和动脉粥样硬化病变的Treg/Teff比值显著增加，斑块稳定，其特征是巨噬细胞含量减少，胶原含量增加。联合治疗还可显著降低脾脏ly6high炎性单核细胞，并可能在动脉粥样硬化病变中诱导有利的巨噬细胞表型改变。我们的研究结果表明，除了抑制Teff反应外，增强Treg介导的免疫反应在预防动脉粥样硬化方面更有效，这为动脉粥样硬化提供了一种新的治疗方法。
Accumulating evidence suggests that the balance between pathogenic effector T cells (Teffs) and regulatory T cells (Tregs) may be important for controlling atherosclerotic disease. We hypothesized that a combination therapy with anti‐CD3 antibody (CD3‐Ab) and IL‐2/anti‐IL‐2 monoclonal antibody complex (IL‐2 complex) aimed at increasing the ratio of Tregs to Teffs would effectively inhibit atherosclerosis in mice. We treated apolipoprotein E‐deficient mice fed a high‐cholesterol diet with vehicle, CD3‐Ab, IL‐2 complex, or their combination. Mice receiving the combination therapy had markedly reduced atherosclerotic lesions than mice treated with CD3‐Ab or IL‐2 complex alone. In addition, a striking increase in the Treg/Teff ratio of lymphoid organs and atherosclerotic lesions, along with plaque stabilization characterized by decreased macrophage content and increased collagen content was observed. The combination treatment also markedly reduced splenic Ly6Chigh inflammatory monocytes and might induce a favorable macrophage phenotype change in atherosclerotic lesions. Our results indicate that in addition to suppressing Teff responses, enhancing Treg‐mediated immune responses is more efficacious in preventing atherosclerosis, suggesting a novel therapeutic approach for atherosclerosis.