Newton Amy H, Benedict Stephen H
Department of Molecular Biosciences, University of Kansas, Lawrence, KS, United States.
Department of Molecular Biosciences, University of Kansas, Lawrence, KS, United States.
Hum Immunol. 2014 Jul;75(7):621-8. doi: 10.1016/j.humimm.2014.04.017. Epub 2014 Apr 24.
Oxidized LDL (oxLDL) in the arterial wall and its incorporation into foam cells leads to inflammation and nucleation of atherosclerotic plaque; this is opposed by HDL. OxLDL and HDL regulate activation of macrophages and endothelial cells, and study of T cell participation has been limited to mature, differentiated cells such as Th1 cells, which perpetuate atherogenesis by promoting cell-mediated responses and inflammation. Immature naïve T cells, just emerged from the thymus, have remained largely unstudied. We hypothesized that LDL and HDL provide selective modulation of immature naïve T cell differentiation and participation in plaque development. In our in vitro model, naïve cells become activated and differentiate to mature effector T cells that are Th1, Th2 or Treg cells. Addition of oxLDL favored differentiation to Th1 cells, reduced Th2 cell activity and prolonged cell survival. In contrast, HDL inhibited T cell proliferation and reduced cell survival. The data suggest a novel mechanism where oxLDL enhances differentiation of human naïve CD4+ T cells to Th1 cells capable of promoting inflammation and plaque progression, and this is opposed by HDL.
动脉壁中的氧化低密度脂蛋白（oxLDL）及其被泡沫细胞摄取会导致炎症和动脉粥样硬化斑块的形成；高密度脂蛋白（HDL）则具有相反作用。oxLDL和HDL调节巨噬细胞和内皮细胞的活化，而对T细胞参与的研究仅限于成熟的、分化的细胞，如Th1细胞，它们通过促进细胞介导的反应和炎症来维持动脉粥样硬化的发展。刚从胸腺中产生的未成熟初始T细胞在很大程度上仍未得到研究。我们推测LDL和HDL对未成熟初始T细胞的分化以及参与斑块形成具有选择性调节作用。在我们的体外模型中，初始细胞被激活并分化为成熟的效应T细胞，即Th1、Th2或调节性T（Treg）细胞。添加oxLDL有利于向Th1细胞分化，降低Th2细胞活性并延长细胞存活时间。相比之下，HDL抑制T细胞增殖并降低细胞存活。这些数据提示了一种新机制，即oxLDL增强人类未成熟CD4 + T细胞向能够促进炎症和斑块进展的Th1细胞的分化，而HDL则起到相反作用。
