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Pathogenesis and etiology of cutaneous NK/T lymphoproliferative disorders

皮肤 NK/T 淋巴细胞增殖性疾病的发病机制和病因学

基本信息

批准号：
11670843
负责人：
IWATSUKI Keiji
金额：
$ 2.24万
依托单位：
Okayama University (2001)Fukushima Medical University (1999-2000)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670843/
关键词：
NK T cell lymphoma EB virus latent infection mosquito hypersensitivity hydroa vacciniforme リンパ腫 NK細胞 vIL-10 免疫応答 virokine viroceptor EBNA遺伝子 LMP-1遺伝子皮膚NK Tリンパ腫ウイルスIL-10

项目摘要

In order to elucidate the EBV gene expression, we examined 8 patients with cutaneous EBV-related NK/T-cell lymphomas, including 6 patients with NK-cell phenotypes and 2 patients with T-cell phenotypes. All samples from the patients contained EBV nuclear antigen(EBNA)-1 mRNA which was transcribed using the Q promoter, whereas both the Q promoter and another upstream promoter (Cp/Wp) were used in 3 EBV-positive cell lines, B95.8, Raji and Jiyoye. Latent membrane protein-1 (LMP-1) mRNA was detected in 7 out of 8 patients and all cell lines, whereas EBNA-2 transcripts were found only in the cell lines. The BHRF1 (viral bcl-2 homologue) and BCRF1 (viral interleukin(vlL)-10) gene transcripts were detected in 1 (NK2) and 2 patients (NK2 and 3), respectively. The patient (NK2) with UK-cell lymphoma expressing the both transcripts died of rapid progression of the illness. No LMP-1, EBNA-2 or ZEBRA antigens were detected in the skin lesions by immunostaining although they were positive in the cell line cells.One EBV-infected NK cellI line designated NOY-1 was established from a patient with hypersensitivity to mosquito bite associated with oligoclonal proliferation of EBV-infected NK cells in the blood. Clonal expansion of the cells was observed in the cutaneous lesions following mosquito bite. The cell line cells contained 7.5 copies of EBV-DNA, and produced high levels of IFN-gamma by stimulation.

为了阐明EBV基因的表达，我们检查了8例皮肤EBV相关的NK/T细胞淋巴瘤，包括6例NK细胞表型和2例T细胞表型患者。来自患者的所有样品均含有使用Q启动子转录的EBV核抗原（EBNA）-1 mRNA，而Q启动子和另一上游启动子（Cp/Wp）均用于3种EBV阳性细胞系B95.8、Raji和Jiyoye中。在8例患者中的7例和所有细胞系中检测到潜伏膜蛋白-1（LMP-1）mRNA，而EBNA-2转录物仅在细胞系中发现。BHRF 1（病毒bcl-2同源物）和BCRF 1（病毒白细胞介素（vIL）-10）基因转录本分别在1例（NK 2）和2例（NK 2和3）患者中检测到。患有表达两种转录物的UK细胞淋巴瘤的患者（NK 2）死于疾病的快速进展。免疫组化结果显示，LMP-1、EBNA-2和ZEBRA抗原均为阳性，但在皮损中均未检测到。在蚊虫叮咬后的皮损中观察到细胞的克隆性扩增。该细胞系细胞含有7.5拷贝的EBV-DNA，并通过刺激产生高水平的IFN-γ。