Departments of Surgery, Interdepartmental Program in Vascular Biology and Therapeutics, Yale University School of Medicine, New Haven, Connecticut, USA.
Arterioscler Thromb Vasc Biol. 2010 Sep;30(9):1795-801. doi: 10.1161/ATVBAHA.109.200758. Epub 2010 Jun 10.
The arterial media, populated by vascular smooth muscle cells (VSMC), is an immunoprivileged compartment and, in contrast to the intima or adventitia containing endothelial cells, is generally spared by inflammatory processes, such as arteriosclerosis. To determine mechanisms of medial immunoprivilege, we investigated the ability of human VSMC versus endothelial cells to activate allogeneic T cells in vitro.
Unlike cultured endothelial cells, cultured VSMC do not activate allogeneic memory CD4 or CD8 T cells and fail to effectively support T-cell proliferation to the polyclonal activator, phytohemagglutinin, consistent with a defect in costimulation function. Although many costimulators are comparably expressed on both cell types, endothelial cells but not VSMC basally express OX40 ligand and upregulate inducible costimulator ligand in response to proinflammatory cytokines. OX40 ligand-transduced, but not control- or inducible costimulator ligand-transduced, VSMC acquire the capacity to stimulate allogeneic memory CD4 T cells to produce cytokines and to proliferate in the presence of supplemental l-tryptophan. OX40 ligand overexpression, although not essential, also enhances allogeneic memory CD8 T-cell responses to VSMC after l-tryptophan supplementation.
The inability of cultured VSMC to activate memory T cells results from a lack of essential costimulators, particularly OX40 ligand, in addition to indoleamine 2,3-dioxygenase-mediated tryptophan depletion.
富含血管平滑肌细胞（VSMC）的动脉中层是一个免疫特惠区，与包含内皮细胞的内膜或外膜不同，它通常免受炎症过程的影响，如动脉粥样硬化。为了确定中层免疫特惠的机制，我们研究了人 VSMC 与内皮细胞在体外激活同种异体 T 细胞的能力。
与培养的内皮细胞不同，培养的 VSMC 不能激活同种异体记忆 CD4 或 CD8 T 细胞，也不能有效支持 T 细胞对多克隆激活剂植物血凝素的增殖，这与共刺激功能缺陷一致。尽管许多共刺激分子在两种细胞类型上的表达相似，但内皮细胞而不是 VSMC 基底表达 OX40 配体，并对促炎细胞因子上调诱导性共刺激配体。OX40 配体转导，但不是对照或诱导性共刺激配体转导的 VSMC 获得刺激同种异体记忆 CD4 T 细胞产生细胞因子和在补充 l-色氨酸存在下增殖的能力。OX40 配体过表达虽然不是必需的，但也增强了 l-色氨酸补充后同种异体记忆 CD8 T 细胞对 VSMC 的反应。
培养的 VSMC 不能激活记忆 T 细胞的原因是缺乏必需的共刺激分子，特别是 OX40 配体，此外还有吲哚胺 2,3-双加氧酶介导的色氨酸耗竭。
