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Abstract：
BACKGROUND: Human T-cell lymphotropic virus type 1 (HTLV-1), also denominated Human T-cell leukemia virus-1, induces immune activation and secretion of proinflammatory cytokines, especially in individuals with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Regulatory T lymphocytes (Tregs) may control of inflammation through the production of regulatory cytokines, including IL10 and TGF-β. In this study we determined the frequencies of CD4 + and CD8 + Tregs in a HAM/TSP population, compared to asymptomatic carriers and uninfected individuals, as well as investigated the profiles of regulatory and inflammatory cytokines.
METHODS: Asymptomatic HTLV-1 carriers and HAM/TSP patients were matched by sex and age. The frequencies of IL10- and/or TGF-β-producing Tregs were quantified by flow cytometry. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to quantify HTLV-1 proviral load and the mRNA expression of cytokines and cellular receptors in peripheral blood mononuclear cells.
RESULTS: Total frequencies of CD4 + Tregs, as well as the IL10-producing CD4 + and CD8 + Treg subsets, were statistically higher in patients with HAM/TSP compared to asymptomatic HTLV-1-infected individuals. In addition, a positive correlation was found between the frequency of CD4 + IL10 + Tregs and proviral load in the HAM/TSP patients evaluated. A positive correlation was also observed between gene expression of proinflammatory versus regulatory cytokines only in HAM / TSP group.
CONCLUSIONS: A higher frequencies of IL10-producing Tregs were identified in patients with HAM/TSP. Imbalanced production of IL10 in relation to TGF-β may contribute to the increased inflammatory response characteristically seen in HAM/TSP patients.
METHODS: Asymptomatic HTLV-1 carriers and HAM/TSP patients were matched by sex and age. The frequencies of IL10- and/or TGF-β-producing Tregs were quantified by flow cytometry. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to quantify HTLV-1 proviral load and the mRNA expression of cytokines and cellular receptors in peripheral blood mononuclear cells.
RESULTS: Total frequencies of CD4 + Tregs, as well as the IL10-producing CD4 + and CD8 + Treg subsets, were statistically higher in patients with HAM/TSP compared to asymptomatic HTLV-1-infected individuals. In addition, a positive correlation was found between the frequency of CD4 + IL10 + Tregs and proviral load in the HAM/TSP patients evaluated. A positive correlation was also observed between gene expression of proinflammatory versus regulatory cytokines only in HAM / TSP group.
CONCLUSIONS: A higher frequencies of IL10-producing Tregs were identified in patients with HAM/TSP. Imbalanced production of IL10 in relation to TGF-β may contribute to the increased inflammatory response characteristically seen in HAM/TSP patients.
摘要：
背景：人类嗜T细胞淋巴细胞病毒1型（HTLV-1），也称为人类T细胞白血病病毒-1，诱导免疫激活和分泌促炎细胞因子，特别是在HTLV-1相关脊髓病/热带痉挛性轻瘫（HAM/TSP）患者中。调节性T淋巴细胞（Tregs）可以通过产生调节性细胞因子来控制炎症，包括IL10和TGF-β。在这项研究中，我们确定了HAM/TSP人群中CD4和CD8Tregs的频率，与无症状携带者和未感染个体相比，以及研究调节和炎症细胞因子的概况。
方法：无症状HTLV-1携带者和HAM/TSP患者按性别和年龄进行匹配。通过流式细胞术定量产生IL10和/或TGF-β的Treg的频率。实时逆转录聚合酶链反应（RT-PCR）用于定量HTLV-1前病毒载量以及外周血单个核细胞中细胞因子和细胞受体的mRNA表达。
结果：CD4+Tregs的总频率，以及产生IL10的CD4+和CD8+Treg亚群，与无症状的HTLV-1感染个体相比，HAM/TSP患者在统计学上较高。此外,在评估的HAM/TSP患者中,CD4+IL10+Tregs的频率与前病毒载量呈正相关.仅在HAM/TSP组中，促炎细胞因子与调节性细胞因子的基因表达之间也观察到正相关。
结论：在HAM/TSP患者中发现了更高频率的IL10产生Treg。与TGF-β相关的IL10的不平衡产生可能导致在HAM/TSP患者中特征性观察到的炎症反应增加。
方法：无症状HTLV-1携带者和HAM/TSP患者按性别和年龄进行匹配。通过流式细胞术定量产生IL10和/或TGF-β的Treg的频率。实时逆转录聚合酶链反应（RT-PCR）用于定量HTLV-1前病毒载量以及外周血单个核细胞中细胞因子和细胞受体的mRNA表达。
结果：CD4+Tregs的总频率，以及产生IL10的CD4+和CD8+Treg亚群，与无症状的HTLV-1感染个体相比，HAM/TSP患者在统计学上较高。此外,在评估的HAM/TSP患者中,CD4+IL10+Tregs的频率与前病毒载量呈正相关.仅在HAM/TSP组中，促炎细胞因子与调节性细胞因子的基因表达之间也观察到正相关。
结论：在HAM/TSP患者中发现了更高频率的IL10产生Treg。与TGF-β相关的IL10的不平衡产生可能导致在HAM/TSP患者中特征性观察到的炎症反应增加。
