Redelman D
Department of Microbiology, University of Nevada, Reno 89557.
Cytometry. 1988 Mar;9(2):156-63. doi: 10.1002/cyto.990090210.
The immunosuppressive drug cyclosporin A (CsA) inhibits mixed lymphocyte responses, blocks the generation of cytotoxic T lymphocytes, and inhibits the T lymphocyte proliferative response stimulated by polyclonal activators such as phytohemagglutinin (PHA). Nevertheless, there have been contradictory reports attempting to explain the mechanism(s) for this immunosuppressive activity. In the current studies, human peripheral blood mononuclear cells (PBM) were stimulated with PHA in the presence or absence of CsA. Flow cytometric examination of PBM loaded with the Ca2+-sensitive dye Indo-1 showed that concentrations of CsA sufficient to inhibit 90-100% of tritiated thymidine incorporation had no effect on the PHA-stimulated increase in the intracellular Ca2+ concentration ([Ca2+]i). Likewise, inhibitory amounts of CsA had virtually no effect on the increase in cell volume that occurs during T lymphocyte activation. These results were not altered by pretreating the PBM with CsA for 30 min at 37 degrees C prior to adding the PHA. On the other hand, inhibitory concentrations of CsA prevented the expression of receptors for T cell growth factor (interleukin-2, IL-2), as measured by monoclonal antibodies to CD25 after 16-24-hr incubation. In like manner, CsA also prevented the increase in the expression of the E-rosette receptor (CD2) on these same cells. If cultures containing PHA and inhibitory amounts of CsA were incubated for 40-72 h, there was partial recovery both of proliferative activity and of the expression of CD25 and CD2. Thus, CsA does not appear to affect the initial activation signal(s), but does interfere with one or more subsequent events necessary to initiate the appearance of "activation antigens."
免疫抑制药物环孢素A（CsA）可抑制混合淋巴细胞反应，阻断细胞毒性T淋巴细胞的产生，并抑制由多克隆激活剂如植物血凝素（PHA）刺激的T淋巴细胞增殖反应。然而，对于这种免疫抑制活性的机制，一直存在相互矛盾的报道。在当前的研究中，在有或没有CsA的情况下，用PHA刺激人外周血单个核细胞（PBM）。对负载有Ca2+敏感染料Indo-1的PBM进行流式细胞术检查表明，足以抑制90%-100%氚标记胸腺嘧啶核苷掺入的CsA浓度对PHA刺激的细胞内Ca2+浓度（[Ca2+]i）升高没有影响。同样，抑制剂量的CsA对T淋巴细胞激活过程中发生的细胞体积增加几乎没有影响。在加入PHA之前，将PBM在37℃下用CsA预处理30分钟，这些结果并未改变。另一方面，在16-24小时孵育后，通过针对CD25的单克隆抗体测量，抑制浓度的CsA可阻止T细胞生长因子（白细胞介素-2，IL-2）受体的表达。同样，CsA也阻止了这些相同细胞上E-玫瑰花结受体（CD2）表达的增加。如果含有PHA和抑制剂量CsA的培养物孵育40-72小时，则增殖活性以及CD25和CD2的表达会部分恢复。因此，CsA似乎不影响初始激活信号，但确实会干扰启动“激活抗原”出现所需的一个或多个后续事件。
