Division of Cardiology, Oppenheimer Atherosclerosis Research Center, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
PLoS One. 2012;7(2):e30780. doi: 10.1371/journal.pone.0030780. Epub 2012 Feb 9.
Immunization of hypercholesterolemic mice with selected apoB-100 peptide antigens reduces atherosclerosis but the precise immune mediators of athero-protection remain unclear. In this study we show that immunization of apoE (-/-) mice with p210, a 20 amino acid apoB-100 related peptide, reduced aortic atherosclerosis compared with PBS or adjuvant/carrier controls. Immunization with p210 activated CD8(+) T cells, reduced dendritic cells (DC) at the site of immunization and within the plaque with an associated reduction in plaque macrophage immunoreactivity. Adoptive transfer of CD8(+) T cells from p210 immunized mice recapitulated the athero-protective effect of p210 immunization in naïve, non-immunized mice. CD8(+) T cells from p210 immunized mice developed a preferentially higher cytolytic response against p210-loaded dendritic cells in vitro. Although p210 immunization profoundly modulated DCs and cellular immune responses, it did not alter the efficacy of subsequent T cell dependent or independent immune response to other irrelevant antigens. Our data define, for the first time, a role for CD8(+) T cells in mediating the athero-protective effects of apoB-100 related peptide immunization in apoE (-/-) mice.
用选定的载脂蛋白 B-100 肽抗原对高胆固醇血症小鼠进行免疫接种可减少动脉粥样硬化，但动脉粥样硬化保护的确切免疫介质仍不清楚。在这项研究中，我们表明，用 p210（一种 20 个氨基酸的载脂蛋白 B-100 相关肽）对 apoE（-/-）小鼠进行免疫接种可减少主动脉粥样硬化，与 PBS 或佐剂/载体对照相比。p210 免疫接种可激活 CD8(+) T 细胞，减少免疫接种部位和斑块中的树突状细胞 (DC)，并与斑块巨噬细胞免疫反应性降低相关。从 p210 免疫小鼠过继转移 CD8(+) T 细胞可重现 p210 免疫在非免疫、未免疫小鼠中的动脉粥样硬化保护作用。来自 p210 免疫小鼠的 CD8(+) T 细胞在体外对负载 p210 的树突状细胞表现出优先更高的细胞毒性反应。尽管 p210 免疫接种显著调节了 DC 和细胞免疫反应，但它并没有改变随后对其他无关抗原的 T 细胞依赖性或非依赖性免疫反应的功效。我们的数据首次定义了 CD8(+) T 细胞在介导载脂蛋白 B-100 相关肽免疫接种对 apoE（-/-）小鼠的动脉粥样硬化保护作用中的作用。
