From the Neurology Service (J.E.M.-R., R.R., E.C., A.O., J.R.) and Immunology Unit (A.M., M.L.-B.), Hospital del Mar Medical Research Institute (IMIM), Universitat Pompeu Fabra, Barcelona, Spain; and Department of Pathology (J.M.-C., T.B., F.A.) and Vascular Surgery Department (L.R.), Hospital del Mar, Universidad Autónoma de Barcelona, Barcelona, Spain.
Arterioscler Thromb Vasc Biol. 2013 Nov;33(11):2653-9. doi: 10.1161/ATVBAHA.113.302163. Epub 2013 Aug 22.
Human cytomegalovirus (HCMV), a pathogen involved in the development and progression of atherosclerosis, promotes in some individuals a marked reconfiguration of the natural killer (NK)-cell compartment whose hallmark is a persistent expansion of a peripheral blood NK-cell subset expressing the CD94/NKG2C NK receptor. We aimed to evaluate whether the HCMV-associated NK-cell compartment reconfiguration is related to carotid atherosclerotic plaque (CAP) instability.
NK receptor expression (ie, LILRB1, NKG2A, NKG2C, and killer immunoglobulin-like receptors [KIR]) by peripheral NK and T cells was evaluated in 40 patients with HCMV+ with CAP, including nonatherosclerotic strokes (n=15) and healthy subjects (n=11) as controls. High-risk CAP (n=16), defined as carotid stenosis >50% with ipsilateral neurological symptomatology in the previous 180 days, compared with non-high-risk CAP had higher %NKG2C+ NK cells (29.5 ± 22.4% versus 16.3 ± 13.2%; P=0.026; odds ratio, 1.053; 95% confidence interval, 1.002-1.106; P=0.042), with a corresponding reduction in the NKG2A+ NK subset (31.7 ± 17.8% versus 41.8 ± 15.8%; P=0.072). The proportions of NKG2C+ NK cells in high-risk CAP were inversely correlated with the CD4+/CD8+ ratio (R(Spearman)=-0.629; P=0.009) and directly with high-sensitivity C-reactive protein levels (R(Pearson) = 0.591; P=0.012), consistent with higher subclinical systemic inflammation. The intraplaque inflammatory infiltrate, evaluated in 27 CAP obtained after endarterectomy, showed a higher presence of subintimal CD3+ lymphocytes in those patients with HCMV-induced changes in the peripheral NK- and T-cell compartments.
The expansion of NKG2C+ NK cells in patients with CAP seems to be associated with an increased risk of plaque destabilization in some patients with chronic HCMV infection.
人类巨细胞病毒（HCMV）是一种参与动脉粥样硬化发生和发展的病原体，它可导致某些个体的自然杀伤（NK）细胞群发生显著的重构，其特征是外周血 NK 细胞亚群的持续扩张，这些细胞表达 CD94/NKG2C NK 受体。我们旨在评估与 HCMV 相关的 NK 细胞群重构是否与颈动脉粥样硬化斑块（CAP）不稳定有关。
我们评估了 40 例伴有 CAP 的 HCMV+患者（包括非动脉粥样硬化性中风患者 15 例和健康对照者 11 例）外周 NK 和 T 细胞的 NK 受体表达（即 LILRB1、NKG2A、NKG2C 和杀伤细胞免疫球蛋白样受体[KIR]）。与非高危 CAP 相比，高危 CAP（定义为颈动脉狭窄>50%，且在过去 180 天内同侧有神经系统症状）的 NKG2C+NK 细胞比例更高（29.5%±22.4%比 16.3%±13.2%；P=0.026；比值比，1.053；95%置信区间，1.002-1.106；P=0.042），而 NKG2A+NK 亚群的比例降低（31.7%±17.8%比 41.8%±15.8%；P=0.072）。高危 CAP 中 NKG2C+NK 细胞的比例与 CD4+/CD8+比值呈负相关（Spearman 相关系数为-0.629；P=0.009），与高敏 C 反应蛋白水平呈正相关（Pearson 相关系数为 0.591；P=0.012），这与亚临床全身性炎症反应更高有关。在 27 例颈动脉内膜切除术获得的 CAP 中评估了斑块内炎症浸润，发现伴有 HCMV 诱导的外周 NK 和 T 细胞群改变的患者，其斑块内 subintimal CD3+淋巴细胞的存在更多。
在伴有 CAP 的患者中，NKG2C+NK 细胞的扩增似乎与某些慢性 HCMV 感染患者斑块不稳定的风险增加有关。
