Hornung N, Raskova J, Raska K, Degiannis D
Department of Pathology, UMDNJ-Robert Wood Johnson Medical School, Piscataway 08854.
Transplantation. 1993 Oct;56(4):985-90. doi: 10.1097/00007890-199310000-00039.
In order to determine which drug may be more effective in clinical abnormalities associated with polyclonal B lymphocyte activation, we compared the in vitro effects of CsA and rapamycin on proliferation or differentiation of preactivated B cells. For that purpose, highly purified B lymphocytes were preactivated in the presence of formalinized Staphylococcus aureus bacteria and then recultured in the presence or in the absence of either rIL-2, rIL-6, or combination or rIL-2 and rIL-6. After 48 hr in culture, S. aureus bacteria upregulated significantly the binding of phycoerythrin-conjugated IL-2 and IL-6, respectively, by purified B lymphocytes, indicating generation and/or upregulation of receptors for these cytokines. Such preactivated B lymphocytes proliferated in response to optimal concentrations of rIL-2, whereas the addition of rIL-6 to preactivated cells was always accompanied by a decrease of the proliferation rate. CsA upregulated cell proliferation when it was added in the second culture period in the presence or in the absence of rIL-6, whereas rapamycin had no effect in these cases. A combination of rIL-2 plus rIL-6 upregulated significantly the proliferative responses of preactivated B cells. In such cultures both CsA and rapamycin had an inhibitory effect on the proliferative responses. IgM production was unaffected by the addition of rIL-6 to cultures of preactivated B cells, whereas addition of rIL-2 and of the IL-2/IL-6 combination enhanced considerably IgM production. Irrespective of cytokines added, CsA upregulated the production of IgM. In contrast, rapamycin inhibited IgM production in all cases. Our results indicate that, in this experimental system, rapamycin is an effective immunosuppressive agent and its use, at least in vitro, is not accompanied by an upregulation of either the proliferation or differentiation of B lymphocytes.
为了确定哪种药物在与多克隆B淋巴细胞活化相关的临床异常中可能更有效，我们比较了环孢素A（CsA）和雷帕霉素对预激活B细胞增殖或分化的体外作用。为此，在福尔马林固定的金黄色葡萄球菌存在下对高度纯化的B淋巴细胞进行预激活，然后在有或无重组白细胞介素-2（rIL-2）、重组白细胞介素-6（rIL-6）、rIL-2与rIL-6组合的情况下进行再培养。培养48小时后，金黄色葡萄球菌分别显著上调了纯化B淋巴细胞对藻红蛋白偶联的IL-2和IL-6的结合，表明这些细胞因子受体的产生和/或上调。这种预激活的B淋巴细胞对最佳浓度的rIL-2有增殖反应，而向预激活细胞中添加rIL-6总是伴随着增殖率的降低。当在第二个培养期添加CsA时，无论有无rIL-6，细胞增殖均上调，而在这些情况下雷帕霉素无作用。rIL-2加rIL-6的组合显著上调了预激活B细胞的增殖反应。在这种培养中，CsA和雷帕霉素对增殖反应均有抑制作用。向预激活B细胞培养物中添加rIL-6不影响IgM产生，而添加rIL-2和IL-2/IL-6组合则显著增强IgM产生。无论添加何种细胞因子，CsA均上调IgM产生。相反，雷帕霉素在所有情况下均抑制IgM产生。我们的结果表明，在这个实验系统中，雷帕霉素是一种有效的免疫抑制剂，其使用至少在体外不会伴随着B淋巴细胞增殖或分化的上调。
