Baiocchi R A, Ross M E, Tan J C, Chou C C, Sullivan L, Haldar S, Monne M, Seiden M V, Narula S K, Sklar J
Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY.
Blood. 1995 Feb 15;85(4):1063-74.
Both human (hu) and viral (v) interleukin-10 (IL-10) appear to be important cofactors in the survival and growth of lymphoblastoid cell lines infected with Epstein-Barr virus (EBV). When mice with severe combined immune deficiency (SCID) are injected with human peripheral blood lymphocytes (PBL) from normal individuals who are seropositive for EBV, the majority of hu-PBL-SCID mice will develop an EBV-associated lymphoproliferative disease (EBV-LPD) of human B-cell origin, not unlike some cases of EBV-LPD that are seen in immunocompromised individuals. The role of huIL-10 or vIL-10 in this chimeric mouse model of EBV-LPD is unknown. In the present study, we show that hu-PBL-SCID mice that develop EBV-LPD have significant elevation of serum huIL-10 levels compared with mice that do not develop EBV-LPD (P = .005). vIL-10 was undetectable in all animals. The EBV+ tumor samples express transcript for huIL-10 and huIL-10 receptor, express huIL-10 protein by immunohistochemical staining, and show specific binding of recombinant (r) huIL-10. In vitro analysis of the functional consequences of rhuIL-10 binding to IL-10 receptors on fresh EBV+ tumor cells shows that rhuIL-10 can prevent programmed cell death as well as promote proliferation and can do so at concentrations of huIL-10 found in vivo. Thus, huIL-10 production by EBV+ tumor cells may contribute directly to their malignant outgrowth in the hu-PBL-SCID mouse by two autocrine mechanisms: prevention of programmed cell death and proliferation. The implications of such findings with regard to EBV-LPD in humans is discussed.
人源（hu）和病毒源（v）白细胞介素-10（IL-10）似乎都是感染爱泼斯坦-巴尔病毒（EBV）的淋巴母细胞系存活和生长的重要辅助因子。当给严重联合免疫缺陷（SCID）小鼠注射来自EBV血清学阳性正常个体的人外周血淋巴细胞（PBL）时，大多数hu-PBL-SCID小鼠会发生人B细胞来源的EBV相关淋巴增殖性疾病（EBV-LPD），这与免疫功能低下个体中所见的某些EBV-LPD病例并无不同。huIL-10或vIL-10在这种EBV-LPD嵌合小鼠模型中的作用尚不清楚。在本研究中，我们发现，与未发生EBV-LPD的小鼠相比，发生EBV-LPD的hu-PBL-SCID小鼠血清huIL-10水平显著升高（P = 0.005）。在所有动物中均未检测到vIL-10。EBV阳性肿瘤样本表达huIL-10及其受体的转录本，通过免疫组织化学染色表达huIL-10蛋白，并显示重组（r）huIL-10的特异性结合。对新鲜EBV阳性肿瘤细胞上rhuIL-10与IL-10受体结合的功能后果进行体外分析表明，rhuIL-10可以预防程序性细胞死亡并促进增殖，并且可以在体内发现的huIL-10浓度下做到这一点。因此，EBV阳性肿瘤细胞产生的huIL-10可能通过两种自分泌机制直接促进其在hu-PBL-SCID小鼠中的恶性生长：预防程序性细胞死亡和增殖。本文讨论了这些发现对人类EBV-LPD的意义。
