Possible origin of adult T-cell leukemia/lymphoma cells from human T lymphotropic virus type-1-infected regulatory T cells
Possible origin of adult T-cell leukemia/lymphoma cells from human T lymphotropic virus type-1-infected regulatory T cells
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DOI：
10.1111/j.1349-7006.2005.00080.x
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发表时间：
2005-08-01
期刊：
影响因子：
5.7
通讯作者：
Matsuyama, T
中科院分区：
文献类型：
--
作者：
Kohno, T;Yamada, Y;Matsuyama, T
成人 T 细胞白血病/淋巴瘤 (ATLL) 是一种由人类 T 淋巴细胞病毒 1 型 (HTLV-1) 引起的淋巴组织增生性疾病。尽管 ATLL 细胞表现出激活的辅助/诱导 T 细胞表型、CD4(+) 和 CD25(+)，但已知它们表现出很强的免疫抑制活性。由于调节性T细胞（Treg细胞）表达CD4（+）和CD25+分子并具有有效的免疫反应抑制活性，我们研究了ATLL细胞和Treg细胞之间可能的联系。在原代ATLL细胞中，Treg细胞标志分子Foxp3和糖皮质激素诱导的肿瘤坏死因子受体家族相关蛋白（GITR）的表达水平显着高于健康成人。此外，ATLL 细胞在体外对刀豆球蛋白 A 刺激无反应，并抑制正常 T 细胞的增殖。 GITR mRNA 表达由 HTLV-1 反式激活蛋白 Tax 诱导，GITR 启动子分析表明，这种诱导取决于假定转录位点上游 -431 bp 至 -444 bp 的 kappa B 位点。综上所述，ATLL 细胞可能起源于 HTLV-1 感染的 Treg 细胞，而 GITR 似乎参与了 ATLL 的进展。
Adult T-cell leukemia/lymphoma (ATLL) is a lymphoproliferative disorder caused by human T lymphotropic virus type 1 (HTLV-1). Although ATLL cells display an activated helper/inducer T-cell phenotype, CD4(+) and CD25(+), they are known to exhibit strong immunosuppressive activity. As regulatory T cells (Treg cells) express CD4(+) and CD25+ molecules and possess potent immune response suppressive activity, we investigated a possible link between ATLL cells and Treg cells. In primary ATLL cells, the expression levels of the Treg cell marker molecules Foxp3 and glucocorticoid-induced tumor necrosis factor receptor family related protein (GITR) were significantly higher than in those from healthy adults. Furthermore, ATLL cells are unresponsive in vitro to concanavalin A stimulation and suppress the proliferation of normal T cells. GITR mRNA expression was induced by the HTLV-1 transactivator Tax, and GITR promoter analyses revealed that this induction depends on the kappa B site from -431 bp to -444 bp upstream of the putative transcription site. Taken together, ATLL cells may originate from HTLV-1-infected Treg cells, and GITR seems to be involved in the progression to ATLL.