Expression of CCR9 in HTLV-1+ T cells and ATL cells expressing tax
Expression of CCR9 in HTLV-1+ T cells and ATL cells expressing tax
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DOI：
10.1002/ijc.22483
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发表时间：
2007-04-01
影响因子：
6.4
通讯作者：
Yoshie, Osamu
中科院分区：
文献类型：
--
作者：
Nagakubo, Daisuke;Jin, Zhe;Yoshie, Osamu
成人t细胞白血病（ATL）是一种高度侵袭性的成熟CD4(+) t细胞恶性肿瘤，其病因学与人类t淋巴细胞嗜病毒I型（HTLV-1）相关。ATL的特点是淋巴结、脾脏、肝脏、皮肤和肠道常浸润。先前，我们和其他人已经表明，大多数ATL病例CCR4强烈阳性，这可能解释了ATL频繁侵袭皮肤的原因。在这里，我们研究了ATL细胞是否表达CCR9，这与t细胞归巢到胃肠道有关。携带HTLV-1的人T细胞系一致表达CCR9和HTLV-1编码的转录激活子Tax。虽然从外周血中新分离的ATL细胞几乎不表达CCR9，但培养1天的ATL细胞一致表达CCR9，同时上调Tax。Cd2+诱导携带Tax的Jurkat人T细胞系JPX-9亚系在金属硫蛋白启动子的控制下表达Tax，导致CCR9表达上调。通过共转染Tax表达载体或Cd2+处理的JPX-9细胞，CCR9启动子控制的荧光素酶报告基因得以表达。此外，免疫组织化学染色显示浸润胃肠道的ATL细胞CCR9经常呈阳性。综上所述，CCR9可诱导表达Tax的ATL细胞，并可能在ATL的胃肠道病变中发挥作用。(c) 2007 Wiley-Liss, Inc。
Adult T-cell leukemia (ATL) is a highly aggressive mature CD4(+) T-cell malignancy that is etiologically associated with human T-lymphotropic virus Type I (HTLV-1). ATL is characterized by frequent infiltration of lymph nodes, spleen, liver, skin and gut. Previously, we and others have shown that the majority of ATL cases are strongly positive for CCR4, which may explain the frequent skin invasion of ATL. Here, we examined whether ATL cells express CCR9, which is involved in T-cell homing to the gastrointestinal tract. Human T cell lines carrying HTLV-1 consistently expressed CCR9 together with the HTLV-1-encoded transcriptional activator Tax. Although ATL cells freshly isolated from peripheral blood hardly expressed CCR9, ATL cells cultured for I day consistently expressed CCR9 in parallel with the upregulation of Tax. Induction of Tax by Cd2+ in JPX-9, a subline of Jurkat human T cell line carrying Tax under the control of metallothionein promoter, led to upregulation of CCR9. A luciferase reporter gene under the control of the CCR9 promoter was expressed by cotransfection of an expression vector for Tax or in Cd2+-treated JPX-9 cells. Furthermore, immunohistochemical staining demonstrated that ATL cells infiltrating gastrointestinal tract were frequently positive for CCR9. Collectively, CCR9 is inducible in ATL cells expressing Tax and may play a role in the gastrointestinal involvement of ATL. (c) 2007 Wiley-Liss, Inc.