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CXCR1 和 CXCR2 在 HTLV-1 携带者和 HTLV-1 相关脊髓病/热带痉挛性截瘫(HAM/TSP)患者中的不同作用。

Different roles of CXCR1 and CXCR2 in HTLV-1 carriers and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients.

机构信息

Immunology Research Center, Division of Inflammation and Inflammatory Diseases, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Med Microbiol Immunol. 2019 Oct;208(5):641-650. doi: 10.1007/s00430-018-0568-8. Epub 2018 Oct 20.

Abstract

One of the prominent features of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is the excessive recruitment of leukocytes to the central nervous system (CNS), which leads to an inflammatory response-with chemokines and their receptors playing the main role in this recruitment. The aim of the study was to examine the relation of CXCR1 and CXCR2, both of which are involved in the trafficking of lymphocytes into the CNS, with the outcome of HTLV-1 infection. The mRNA levels of CXCR1 and CXCR2 were examined in peripheral blood mononuclear cells (PBMCs) of HAM/TSP patients, HTLV-1 asymptomatic carriers (ACs), and healthy controls (HCs). Furthermore, the frequency of CD4 and CD8 T cells expressing CXCR1 and CXCR2 was evaluated in the studied groups. The results of the present study showed a substantial increase in the mean mRNA expression of CXCR2 in the HAM/TSP patients compared to the HCs and ACs (p < 0.001). A positive correlation was also found between PVL and CXCR2 mRNA expression in the total population of HTLV-1-infected subjects (R = 0.526, p < 0.001). Moreover, the percentage of CD8 CXCR2-expressing cells was higher in HAM/TSP patients compared to ACs and HCs (p < 0.05, p < 0.01, respectively). Although the percentage of CD4 CXCR2-expressing cells was higher in HAM/TSP patients than in ACs and HCs, a significant difference was only found between HAM/TSP patients and HCs (p < 0.05). No significant difference in the CXCR1 mRNA expression was observed in the studied groups. The frequency of the CD8 CXCR1- and CD4 CXCR1-expressing cells was significantly lower in HAM/TSP patients than in ACs and HCs (p < 0.001 and p < 0.01, respectively). In conclusion, the high frequency of CXCR2 CD8 T cells and the high levels of CXCR2 mRNA expression in HAM/TSP patients are associated with disease pathogenesis, while the high frequencies of CXCR1 T cells in ACs might suggest that these cells act as effector CD8 T cells and are involved in controlling the viral spread and modulation of the immune response.

摘要

HTLV-1 相关脊髓病/热带痉挛性截瘫 (HAM/TSP) 的一个突出特征是白细胞大量募集到中枢神经系统 (CNS),导致炎症反应——趋化因子及其受体在这种募集中起主要作用。本研究旨在研究参与淋巴细胞向中枢神经系统转运的趋化因子受体 1 (CXCR1) 和趋化因子受体 2 (CXCR2) 与 HTLV-1 感染结局的关系。检测 HAM/TSP 患者、HTLV-1 无症状携带者 (AC) 和健康对照 (HC) 的外周血单个核细胞 (PBMC) 中 CXCR1 和 CXCR2 的 mRNA 水平。此外,还评估了研究组中表达 CXCR1 和 CXCR2 的 CD4 和 CD8 T 细胞的频率。本研究结果显示,与 HC 和 AC 相比,HAM/TSP 患者的 CXCR2 平均 mRNA 表达显著增加 (p<0.001)。在 HTLV-1 感染受试者的总人群中还发现了 PVL 与 CXCR2 mRNA 表达之间的正相关 (R=0.526,p<0.001)。此外,与 AC 和 HC 相比,HAM/TSP 患者的 CD8 CXCR2 表达细胞百分比更高 (p<0.05,p<0.01)。尽管 HAM/TSP 患者的 CD4 CXCR2 表达细胞百分比高于 AC 和 HC,但仅在 HAM/TSP 患者与 HC 之间存在显著差异 (p<0.05)。在研究组中未观察到 CXCR1 mRNA 表达的显著差异。与 AC 和 HC 相比,HAM/TSP 患者的 CD8 CXCR1 和 CD4 CXCR1 表达细胞频率显著降低 (p<0.001 和 p<0.01)。总之,HAM/TSP 患者中 CXCR2 CD8 T 细胞的高频率和 CXCR2 mRNA 表达水平与疾病发病机制相关,而 AC 中 CXCR1 T 细胞的高频率可能表明这些细胞作为效应 CD8 T 细胞发挥作用,参与控制病毒传播和免疫反应的调节。

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