Drexler H G, Uphoff C C, Gaidano G, Carbone A
DSMZ-German Collection of Microorganisms and Cell Cultures, Department of Human and Animal Cell Cultures, Braunschweig.
Leukemia. 1998 Oct;12(10):1507-17. doi: 10.1038/sj.leu.2401160.
Primary effusion lymphoma (PEL; also known as body cavity-based lymphoma) is recognized as a new and unique lymphoma entity occurring predominantly, but not exclusively in human immunodeficiency virus (HIV)-seropositive patients with acquired immunodeficiency syndrome (AIDS). PEL grows exclusively in body cavities as serous lymphomatous effusion without evidence of mass disease or dissemination. Their most unique feature is infection with the newly discovered human herpesvirus-8 (HHV-8; also known as Kaposi's sarcoma-associated herpesvirus), often accompanied by co-infection with Epstein-Barr virus (EBV). A number of continuous lymphoma cell lines have been established from the malignant pleural effusion, ascitic fluid and peripheral blood of patients with AIDS- and non-AIDS-associated PEL. While all cell lines are HHV-8+, about half of them also contain EBV sequences. Stimulation of the cell lines causes switch from latent to lytic HHV-8 infection. The cells are generally negative for T and B cell immunomarkers (except for CD138 suggesting a pre- or terminal plasma cell stage) and positive for some activation and adhesion markers; they are genotypically B cells with their immunoglobulin genes rearranged. Complex, hyperdiploid karyotypes with multiple structural abnormalities are seen in the cell lines examined. No alterations of known proto-oncogenes are detected in PEL, with the exception of BCL-6 mutations occurring in a large percentage of cases. Heterotransplantation of the cell lines into immunodeficient mice leads to the development of lymphomatous effusion and marked angiogenesis. As HHV-8 contains DNA sequences of several protein homologues, the cell lines express various cytokines, cytokine receptors, chemokines, cell cycle and anti-apoptosis modulators which are upregulated upon stimulation. Indeed, some cell lines produce high levels of (human) interleukin-6 and interleukin-10. Taken together, these cell lines represent very important model systems for the elucidation of the pathobiology of PEL; furthermore, the cell lines are extremely useful scientific tools providing a resource to pursue studies of HHV-8-mediated pathogenic mechanisms.
原发性渗出性淋巴瘤（PEL；也称为体腔淋巴瘤）被认为是一种新的独特淋巴瘤实体，主要但并非仅发生于获得性免疫缺陷综合征（AIDS）的人类免疫缺陷病毒（HIV）血清阳性患者中。PEL仅在体腔内以浆液性淋巴瘤性渗出液的形式生长，无肿块性疾病或播散的证据。其最独特的特征是感染新发现的人类疱疹病毒8型（HHV-8；也称为卡波西肉瘤相关疱疹病毒），常伴有EB病毒（EBV）的共同感染。已从艾滋病相关和非艾滋病相关PEL患者的恶性胸腔积液、腹水和外周血中建立了许多连续的淋巴瘤细胞系。虽然所有细胞系均为HHV-8阳性，但其中约一半也含有EBV序列。对细胞系的刺激会导致HHV-8感染从潜伏状态转变为裂解状态。这些细胞通常对T和B细胞免疫标志物呈阴性（除提示前浆细胞或终末浆细胞阶段的CD138外），对一些激活和黏附标志物呈阳性；它们在基因分型上是B细胞，其免疫球蛋白基因发生了重排。在所检测的细胞系中可见复杂的超二倍体核型，伴有多种结构异常。在PEL中未检测到已知原癌基因的改变，但在很大比例的病例中发生了BCL-6突变。将细胞系异种移植到免疫缺陷小鼠中会导致淋巴瘤性渗出液的形成和明显的血管生成。由于HHV-8含有几种蛋白质同源物的DNA序列，这些细胞系表达各种细胞因子、细胞因子受体、趋化因子、细胞周期和抗凋亡调节剂，这些在受到刺激后会上调。实际上，一些细胞系会产生高水平的（人）白细胞介素-6和白细胞介素-10。综上所述，这些细胞系是阐明PEL病理生物学的非常重要的模型系统；此外，这些细胞系是极其有用的科学工具，为研究HHV-8介导的致病机制提供了资源。
