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人高血压中免疫衰老的 CD8+ T 细胞和 C-X-C 趋化因子受体 3 趋化因子增加。

Immunosenescent CD8+ T cells and C-X-C chemokine receptor type 3 chemokines are increased in human hypertension.

机构信息

Cardiology Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea.

出版信息

Hypertension. 2013 Jul;62(1):126-33. doi: 10.1161/HYPERTENSIONAHA.113.00689. Epub 2013 May 28.

Abstract

The pathogenic role of T cells in hypertension has been documented well in recent animal studies. However, the existence of T-cell-driven inflammation in human hypertension has not been confirmed. Therefore, we undertook immunologic characterization of T cells from patients with hypertension and measured circulating levels of C-X-C chemokine receptor type 3 chemokines, which are well-known tissue-homing chemokines for T cells. We analyzed immunologic markers on T cells from patients with hypertension by multicolor flow cytometry. We then measured circulating levels of the C-X-C chemokine receptor type 3 chemokines, monokine induced by γ interferon (IFN), IFN γ-induced protein 10, and IFN-inducible T-cell α chemoattractant, in patients with hypertension and in age- and sex-matched control subjects by the cytometric bead array method. In addition, we examined histological features of IFN-inducible T-cell α chemoattractant expression from renal biopsy specimens of patients with hypertensive nephrosclerosis and control subjects. The total T-cell population from patients with hypertension showed an increased fraction of immunosenescent, proinflammatory, cytotoxic CD8(+) T cells. Circulating levels of C-X-C chemokine receptor type 3 chemokines were significantly higher in patients with hypertension than in control subjects. Furthermore, immunohistochemical staining revealed increased expression of the T-cell chemokine, IFN-inducible T-cell α chemoattractant, in the proximal and distal tubules of patients with hypertensive nephrosclerosis. Immunosenescent CD8(+) T cells and C-X-C chemokine receptor type 3 chemokines are increased in human hypertension, suggesting a role for T-cell-driven inflammation in hypertension. A more detailed characterization of CD8(+) T cells may offer new opportunities for the prevention and treatment of human hypertension.

摘要

T 细胞在高血压中的致病作用在最近的动物研究中得到了很好的证明。然而,人类高血压中 T 细胞驱动的炎症是否存在尚未得到证实。因此,我们对高血压患者的 T 细胞进行了免疫学特征分析,并测量了循环中 C-X-C 趋化因子受体 3 趋化因子的水平,这些趋化因子是众所周知的 T 细胞组织归巢趋化因子。我们通过多色流式细胞术分析了高血压患者 T 细胞的免疫标志物。然后,我们通过细胞计数珠阵列法测量了高血压患者和年龄及性别匹配的对照者循环中 C-X-C 趋化因子受体 3 趋化因子、γ干扰素(IFN)诱导的单核因子、IFNγ诱导蛋白 10 和 IFN 诱导的 T 细胞 α趋化因子的水平。此外,我们还检查了高血压性肾硬化症患者和对照者肾活检标本中 IFN 诱导的 T 细胞α趋化因子表达的组织学特征。高血压患者的总 T 细胞群体表现出免疫衰老、促炎、细胞毒性 CD8+T 细胞的比例增加。高血压患者的循环 C-X-C 趋化因子受体 3 趋化因子水平明显高于对照者。此外,免疫组织化学染色显示高血压性肾硬化症患者近端和远端肾小管中 T 细胞趋化因子 IFN 诱导的 T 细胞α趋化因子表达增加。免疫衰老的 CD8+T 细胞和 C-X-C 趋化因子受体 3 趋化因子在人类高血压中增加,提示 T 细胞驱动的炎症在高血压中起作用。对 CD8+T 细胞的更详细特征分析可能为人类高血压的预防和治疗提供新的机会。

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