High T-cell response to human cytomegalovirus induces chemokine-mediated endothelial cell damage
High T-cell response to human cytomegalovirus induces chemokine-mediated endothelial cell damage
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DOI：
10.1182/blood-2007-03-078881
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发表时间：
2007-09-15
期刊：
影响因子：
20.3
通讯作者：
Spector, Stephen A.
中科院分区：
文献类型：
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作者：
Bolovan-Fritts, Cynthia A.;Trout, Rodney N.;Spector, Stephen A.
人巨细胞病毒（CMV）感染与涉及血管内皮损伤的炎性疾病有关，包括血管疾病和慢性移植排斥。我们以前报道过，宿主CD 4（+）T细胞对内皮细胞呈递的CMV抗原的反应可以产生干扰素-γ和肿瘤坏死因子-α，其水平足以驱动内皮细胞中炎症的关键标志物fractalkine的诱导。在这项工作中，我们报告说，与CMV特异性T细胞水平低的供体（低反应者）相比，CMV特异性T细胞频率高的供体（高反应者）诱导更高水平的活化相关趋化因子，如fractalkine，RANTES（调节活化，正常T细胞表达和分泌），巨噬细胞炎性蛋白-1 β，以及内皮细胞中的细胞粘附标志物。高反应培养物具有更高水平的白细胞募集和粘附于内皮单层，与内皮细胞的进行性损伤和损失相关。这些导致内皮破坏的过程只需要病毒抗原，而不需要感染性病毒。我们的研究结果进一步支持CMV可能代表一类持久性病原体的成员，其中高抗原特异性T细胞应答定义了慢性炎症和内皮细胞损伤发展的重要风险因素。
Human cytomegalovirus (CMV) infection has been linked to inflammatory diseases that involve vascular endothelial damage, including vascular disease and chronic transplant rejection. We previously reported that the host CD4(+) T-cell response to CMV antigen presented by endothelial cells can produce interferon-gamma and tumor necrosis factor-a at levels sufficient to drive induction of fractalkine, a key marker of inflammation, in endothelial cells. In this work, we report that donors with high frequencies of antigen-specific T cells to CMV (high responders) induce higher levels of activation-associated chemokines such as fractalkine, RANTES (regulated on activation, normal T cell expressed and secreted), and macrophage inflammatory protein-1 beta, together with cell-adhesion markers in endothelial cells compared with donors with low levels of CMV-specific T cells (low responders). High-responder cultures had higher levels of leukocyte recruitment and adherence to the endothelial monolayers associated with progressive damage and loss of the endothelial cells. These processes that led to endothelial destruction only required viral antigen and did not require infectious virus. Our findings further support that CMV may represent one member of a class of persistent pathogens in which a high antigen-specific T-cell response defines an important risk factor for development of chronic inflammation and endothelial cell injury.