BACKGROUND EOS plays an important role in maintaining the suppressive function of regulatory T cells (Tregs), and induces a regulated transformation of Tregs into T helper-like cells, which are capable of secreting proinflammatory cytokines in response to specific inflammatory signals. Meanwhile, significant reduction in Treg activity along with production of proinflammatory cytokines has been reported in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). METHODS In this study, to examine whether there is an alteration in EOS expression in peripheral blood mononuclear cells (PBMCs) derived from HTLV-1-infected individuals especially HAM/TSP, we investigated the expression of HTLV-1 tax genotype, proviral load (PVL), and the mRNA expression of tax, HBZ and EOS in HTLV-1 infected individuals including adult T-cell leukemia/lymphoma (ATL), HAM/TSP, or asymptomatic carriers. The expression levels of EOS mRNA and protein in various HTLV-1-infected or uninfected human T-cell lines were also investigated. RESULTS EOS was highly expressed at the protein level in most HTLV-1 infected T-cell lines, and was augmented after the HTLV-1 regulatory factor Tax was induced in a Tax-inducible JPX-9 cell line. Immunoprecipitation experiments demonstrated a physical interaction between EOS and the viral regulatory protein Tax, but not HBZ. Meanwhile, there was a significant decrease in EOS mRNA levels in PBMCs of HTLV-1 infected individuals irrespective of their clinical statuses. We found an inverse correlation between EOS mRNA levels and HTLV-1 PVL in ATL patients, and positive correlations between both EOS mRNA load and PVL, and EOS and HBZ mRNA load in HAM/TSP patients, whereas this correlation was not observed in other clinical statuses. CONCLUSIONS These findings suggest that both Tax and HBZ can alter the expression of EOS through undetermined mechanisms, and dysregulated expression of EOS in PBMCs of HTLV-1 infected individuals may contribute to the pathological progression of HTLV-1-associated diseases, such as ATL and HAM/TSP.

中文翻译：

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Eka，一种Ikaros家族的锌指转录因子，与HTLV-1癌蛋白Tax相互作用，并且在HTLV-1感染者的外周血单核细胞中被下调，而与临床状况无关。

背景技术EOS在维持调节性T细胞（Tregs）的抑制功能中起着重要作用，并诱导Tregs向T型辅助细胞的调节转化，该细胞能够响应特定的炎症信号而分泌促炎性细胞因子。同时，据报道患有HTLV-1相关性脊髓病/热带痉挛性轻瘫（HAM / TSP）的患者中Treg活性显着降低，并产生促炎细胞因子。方法在这项研究中，为了研究HTLV-1感染基因型，前病毒载量（HTLV-1）的表达在HTLV-1感染者尤其是HAM / TSP衍生的外周血单个核细胞（PBMC）中EOS表达是否存在改变。 PVL），以及tax的mRNA表达，HTLV-1感染者的HBZ和EOS，包括成人T细胞白血病/淋巴瘤（ATL），HAM / TSP或无症状携带者。还研究了在各种HTLV-1感染或未感染的人T细胞系中EOS mRNA和蛋白的表达水平。结果EOS在大多数被HTLV-1感染的T细胞系中在蛋白质水平上高表达，并且在可诱导Tax的JPX-9细胞系中诱导HTLV-1调节因子Tax后，EOS增强。免疫沉淀实验表明EOS与病毒调节蛋白Tax（而非HBZ）之间存在物理相互作用。同时，不论其临床状况如何，HTLV-1感染者的PBMC中EOS mRNA水平均显着下降。我们发现ATL患者EOS mRNA水平与HTLV-1 PVL呈负相关，与HAM / TSP患者的EOS mRNA负载和PVL以及EOS和HBZ mRNA负载之间呈正相关，而在其他临床状况中未观察到这种相关性。结论这些发现表明，Tax和HBZ均可通过不确定的机制改变EOS的表达，并且HTLV-1感染者的PBMC中EOS的表达失调可能与HTLV-1相关疾病的病理进展有关，例如ATL和HBZ。 HAM / TSP。