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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >T lymphocytes from human atherosclerotic plaques recognize oxidized low density lipoprotein.
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T lymphocytes from human atherosclerotic plaques recognize oxidized low density lipoprotein.

机译：来自人动脉粥样斑块的T淋巴细胞识别氧化的低密度脂蛋白。

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摘要

Atherosclerosis, an underlying cause of myocardial infarction, stroke, and other cardiovascular diseases, consists of focal plaques characterized by cholesterol deposition, fibrosis, and inflammation. The presence of activated T lymphocytes and macrophages and high expression of HLA class II molecules are indicative of a local immunologic activation in the atherosclerotic plaque, but the antigen(s) involved has not yet been identified. We established T-cell clones from human atherosclerotic plaques using polyclonal mitogens as stimuli and exposed the clones to potential antigens in the presence of autologous monocytes as antigen-presenting cells. Four of the 27 CD4+ clones responded to oxidized low density lipoprotein (oxLDL) by proliferation and cytokine secretion; this response was dependent on autologous antigen-presenting cells and restricted by HLA-DR. All clones that responded to oxLDL secreted interferon gamma upon activation, but only one produced interleukin 4, suggesting that the response to oxLDL results in immune activation and inflammation but may not be a strong stimulus to antibody production. No significant response to oxLDL could be detected in CD4+ T-cell clones derived from the peripheral blood of the same individuals. Together, the present data suggest that the inflammatory infiltrate in the atherosclerotic plaque is involved in a T-cell-dependent, autoimmune response to oxLDL.
机译：动脉粥样硬化是心肌梗塞，中风和其他心血管疾病的根本原因，由以胆固醇沉积，纤维化和炎症为特征的局部斑块组成。活化的T淋巴细胞和巨噬细胞的存在以及HLA II类分子的高表达表明动脉粥样硬化斑块中存在局部免疫活化，但尚未鉴定出所涉及的抗原。我们使用多克隆有丝分裂原作为刺激物，从人的动脉粥样硬化斑块中建立了T细胞克隆，并在自体单核细胞作为抗原呈递细胞的情况下将克隆暴露于潜在的抗原。 27个CD4 +克隆中有4个通过增殖和细胞因子分泌对氧化型低密度脂蛋白（oxLDL）作出反应；这种反应取决于自体抗原呈递细胞，并受HLA-DR限制。响应oxLDL的所有克隆在激活后都会分泌干扰素γ，但是只有一个会产生白介素4，这表明对oxLDL的响应会导致免疫激活和炎症，但可能不是对抗体产生的强烈刺激。在源自相同个体外周血的CD4 + T细胞克隆中，未检测到对oxLDL的显着反应。总之，本数据表明，动脉粥样硬化斑块中的炎性浸润参与了对oxLDL的T细胞依赖性自身免疫反应。

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