Kanno H, Naka N, Yasunaga Y, Iuchi K, Yamauchi S, Hashimoto M, Aozasa K
Department of Pathology, Osaka University Medical School, Suita, Japan.
Am J Pathol. 1997 Jan;150(1):349-57.
Malignant lymphomas frequently develop in the pleural cavity of patients with long-standing pyothorax. Thus, the term pyothorax-associated lymphoma (PAL) has been proposed for this type of tumor. Most PALs are diffuse lymphomas of B cell type and contain Epstein-Barr virus (EBV) DNA. We have established two lymphoma cell lines from the biopsy specimens of PAL cases, OPL-1 and OPL-2. Both cell lines contain EBV DNA, but only OPL-1 expresses EBV nuclear antigen 2, which works as a target molecule for the cell-mediated immune response. As systemic immunodeficiency is unlikely to be present in PAL patients, PAL from which OPL-1 derived was not expected to be fully developed. In this study, we examined the expression of immunosuppressive factors in OPLs. Only OPL-1, not OPL-2, expressed interleukin-10 (IL-10) mRNA and secreted IL-10 into culture supernatant. Both OPL-1 and OPL-2 expressed transforming growth factor (TGF)-beta 1 mRNA; however, neither expressed latent TGF-beta-binding protein mRNA at a detectable level by Northern blot analysis. Because TGF-beta expresses its functions in cooperation with latent TGF-beta-binding protein, the biological functions of TGF-beta 1 could be negligible. Neither cell line expressed at a detectable level EBV BCRF-1 mRNA, a viral gene product that is partly homologous to human IL-10 and shares biological activities of IL-10. Although IL-10 is reported to promote the growth of activated or neoplastic B cells, OPL-1 did not respond to human recombinant IL-10 by growing faster. As OPL-1 expresses a target antigen for the host cytotoxic T-cell response, the production of an immuno-suppressive cytokine, IL-10, might contribute to the development of overt lymphoma by inducing locally immunosuppressive circumstances. The present study suggests that an immunosuppressive cytokine plays a role in lymphomagenesis of immunocompetent patients.
恶性淋巴瘤常发生于长期脓胸患者的胸腔内。因此，已提出将这种类型的肿瘤称为脓胸相关性淋巴瘤（PAL）。大多数PAL是B细胞型弥漫性淋巴瘤，且含有EB病毒（EBV）DNA。我们从PAL病例的活检标本中建立了两个淋巴瘤细胞系，即OPL-1和OPL-2。两个细胞系均含有EBV DNA，但只有OPL-1表达EBV核抗原2，该抗原作为细胞介导免疫反应的靶分子。由于PAL患者不太可能存在全身性免疫缺陷，因此预计源自OPL-1的PAL尚未完全发展。在本研究中，我们检测了OPL中免疫抑制因子的表达。只有OPL-1，而不是OPL-2，表达白细胞介素-10（IL-10）mRNA并将IL-10分泌到培养上清液中。OPL-1和OPL-2均表达转化生长因子（TGF）-β1 mRNA；然而，通过Northern印迹分析，两者均未在可检测水平表达潜伏性TGF-β结合蛋白mRNA。由于TGF-β与潜伏性TGF-β结合蛋白协同发挥功能，因此TGF-β1的生物学功能可能微不足道。两个细胞系均未在可检测水平表达EBV BCRF-1 mRNA，该病毒基因产物与人IL-10部分同源并具有IL-10的生物学活性。尽管有报道称IL-10可促进活化或肿瘤性B细胞的生长，但OPL-1对人重组IL-10并无生长加快的反应。由于OPL-1表达宿主细胞毒性T细胞反应的靶抗原，免疫抑制细胞因子IL-10的产生可能通过诱导局部免疫抑制环境而有助于明显淋巴瘤的发生。本研究表明，免疫抑制细胞因子在免疫功能正常患者的淋巴瘤发生中起作用。
