Frequent expression of interleukin-10 by Epstein-Barr virus-harboring tumor cells of Hodgkin's disease
Frequent expression of interleukin-10 by Epstein-Barr virus-harboring tumor cells of Hodgkin's disease
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DOI：
10.1182/blood.v87.7.2918.bloodjournal8772918
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发表时间：
1996-04-01
期刊：
影响因子：
20.3
通讯作者：
Stein, H
中科院分区：
文献类型：
--
作者：
Herbst, H;Foss, HD;Stein, H
EB病毒（EBV）相关的霍奇金病（HD）的肿瘤细胞表达病毒蛋白，潜伏感染膜蛋白-1（LMP 1），但逃避通常针对该抗原的细胞毒性反应。我们测试了局部产生的免疫调节白细胞介素（IL）-4和-10是否可能在这一过程中发挥作用。在所有HD病例中均未检测到IL-4 RNA。相比之下，同位素原位杂交和EBV基因产物的存在的相关性显示，与LMP 1阴性HD病例（37例中的6例，16%）相比，LMP 1阳性（26例中的17例，66%）中IL-10表达肿瘤细胞的病例比例显著较高。EBVBRF 1 RNA的缺失表明转录本来源于细胞IL-10基因。类似地，在AIDS相关的恶性非霍奇金淋巴瘤（ARL）中发现了IL-10表达与肿瘤细胞的EBV感染之间的关联。非常小比例的EBV感染的细胞，主要是原始细胞，在传染性单核细胞增多症扁桃体中表达IL-10。因此，虽然不完全排除EBV阳性病例，但IL-10表达经常与HD和ARL中的EBV感染相关，并且似乎被EBV上调，最可能通过LMP 1。鉴于IL-10对细胞介导的免疫的既定抑制作用，表明IL-10表达可能有助于逃避LMP 1阳性细胞针对病毒抗原的细胞毒性。(C)1996年，美国血液学会。
Tumor cells of Epstein-Barr virus (EBV)-associated Hodgkin's disease (HD) express the viral protein, latent infection membrane protein-1 (LMP1), but evade cytotoxic responses normally directed at this antigen. We tested whether local production of the immunoregulatory interleukins (IL)-4 and -10 may have a role in this process. IL-4 RNA was not detectable in any of the HD cases. By contrast, isotopic in situ hybridization and correlation with the presence of EBV gene products showed significantly higher proportions of cases with IL-10 expressing tumor cells in LMP1-positive (17 of 26, 66%) as compared with LMP1-negative HD cases (six of 37, 16%). Absence of EBV BCRF1 RNA indicated that the transcripts originated from the cellular IL-10 gene. Similarly, an association between IL-10 expression and EBV-infection of tumor cells was found in AIDS-related malignant non-Hodgkin lymphomas (ARL). Very small proportions of EBV-infected cells, mainly blasts, expressed IL-10 in infectious mononucleosis tonsils, Thus, although not entirely exclusive to EBV-positive cases, IL-10 expression is frequently associated with EBV-infection in HD and ARL and appears to be upregulated by EBV, most likely through LMP1. In view of the established inhibitory effects of IL-10 on cell mediated immunity, it is suggested that IL-10 expression may contribute to evasion of LMP1-positive cells from cytotoxicity directed at viral antigens. (C) 1996 by The American Society of Hematology.