BACKGROUND CD4+CD25high regulatory T (TReg) cells modulate antigen-specific T cell responses, and can suppress anti-viral immunity. In HTLV-1 infection, a selective decrease in the function of TReg cell mediated HTLV-1-tax inhibition of FOXP3 expression has been described. The purpose of this study was to assess the frequency and phenotype of TReg cells in HTLV-1 asymptomatic carriers and in HTLV-1-associated neurological disease (HAM/TSP) patients, and to correlate with measures of T cell activation. RESULTS We were able to confirm that HTLV-I drives activation, spontaneous IFNgamma production, and proliferation of CD4+ T cells. We also observed a significantly lower proportion of CTLA-4+ TReg cells (CD4+CD25high T cells) in subjects with HAM/TSP patients compared to healthy controls. Ki-67 expression was negatively correlated to the frequency of CTLA-4+ TReg cells in HAM/TSP only, although Ki-67 expression was inversely correlated with the percentage of CD127low TReg cells in healthy control subjects. Finally, the proportion of CD127low TReg cells correlated inversely with HTLV-1 proviral load. CONCLUSION Taken together, the results suggest that TReg cells may be subverted in HAM/TSP patients, which could explain the marked cellular activation, spontaneous cytokine production, and proliferation of CD4+ T cells, in particular those expressing the CD25highCD127low phenotype. TReg cells represent a potential target for therapeutic intervention for patients with HTLV-1-related neurological diseases.

中文翻译：

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在 HTLV-1 感染和 HTLV-1 相关脊髓病/热带痉挛性下肢轻瘫中，CD127low 表达 CD4+CD25high T 调节细胞的频率与人类 T 淋巴细胞营养型病毒 1 (HTLV-1) 前病毒载量呈负相关。

背景 CD4+CD25高调节性T（TReg）细胞调节抗原特异性T细胞反应，并能抑制抗病毒免疫。在 HTLV-1 感染中，已经描述了 TReg 细胞介导的 HTLV-1-tax 抑制 FOXP3 表达的功能的选择性降低。本研究的目的是评估 HTLV-1 无症状携带者和 HTLV-1 相关神经系统疾病 (HAM/TSP) 患者中 TReg 细胞的频率和表型，并与 T 细胞活化的测量相关联。结果我们能够证实HTLV-I驱动CD4+T细胞的活化、自发IFNγ产生和增殖。我们还观察到，与健康对照相比，HAM/TSP 患者的 CTLA-4+ TReg 细胞（CD4+CD25high T 细胞）比例显着降低。Ki-67 表达仅与 HAM/TSP 中 CTLA-4+ TReg 细胞的频率呈负相关，尽管 Ki-67 表达与健康对照受试者中 CD127low TReg 细胞的百分比呈负相关。最后，CD127low TReg 细胞的比例与 HTLV-1 前病毒载量呈负相关。结论 综上所述，结果表明 TReg 细胞可能在 HAM/TSP 患者中被破坏，这可以解释显着的细胞活化、自发细胞因子产生和 CD4+ T 细胞的增殖，特别是那些表达 CD25highCD127low 表型的细胞。TReg 细胞代表了对 HTLV-1 相关神经系统疾病患者进行治疗干预的潜在目标。尽管 Ki-67 表达与健康对照受试者中 CD127low TReg 细胞的百分比呈负相关。最后，CD127low TReg 细胞的比例与 HTLV-1 前病毒载量呈负相关。结论 综上所述，结果表明 TReg 细胞可能在 HAM/TSP 患者中被破坏，这可以解释显着的细胞活化、自发细胞因子产生和 CD4+ T 细胞的增殖，特别是那些表达 CD25highCD127low 表型的细胞。TReg 细胞代表了对 HTLV-1 相关神经系统疾病患者进行治疗干预的潜在目标。尽管 Ki-67 表达与健康对照受试者中 CD127low TReg 细胞的百分比呈负相关。最后，CD127low TReg 细胞的比例与 HTLV-1 前病毒载量呈负相关。结论 综上所述，结果表明 TReg 细胞可能在 HAM/TSP 患者中被破坏，这可以解释显着的细胞活化、自发细胞因子产生和 CD4+ T 细胞的增殖，特别是那些表达 CD25highCD127low 表型的细胞。TReg 细胞代表了对 HTLV-1 相关神经系统疾病患者进行治疗干预的潜在目标。这可以解释显着的细胞活化、自发细胞因子产生和 CD4+ T 细胞的增殖，特别是那些表达 CD25high CD127low 表型的细胞。TReg 细胞代表了对 HTLV-1 相关神经系统疾病患者进行治疗干预的潜在目标。这可以解释显着的细胞活化、自发细胞因子产生和 CD4+ T 细胞的增殖，特别是那些表达 CD25high CD127low 表型的细胞。TReg 细胞代表了对 HTLV-1 相关神经系统疾病患者进行治疗干预的潜在目标。