Granelli-Piperno A, Inaba K, Steinman R M
J Exp Med. 1984 Dec 1;160(6):1792-802. doi: 10.1084/jem.160.6.1792.
Three-day, concanavalin A-induced T lymphoblasts have been used as a model to study lymphokine release from sensitized T cells. The blasts responded to interleukin 2 (IL-2) but did not constitutively produce this or other lymphokines. After mitogen restimulation, blast cells synthesized IL-2 as well as gamma-interferon, B cell-stimulating factor(s), and cytolytic differentiation factor(s). This production resulted from the induction of biologically active lymphokine mRNA. Cyclosporin A (CSA), a potent immunosuppressive agent, strongly inhibited synthesis of IL-2, gamma-interferon, and B cell- and CTL-stimulating factor(s), from mitogen-restimulated T blasts. In contrast, CSA did not block the cytolytic activity of the T blasts, nor modify bulk protein synthesis induced by Con A. CSA also blocked lymphokine release from a phorbol myristate acetate-stimulated thymoma cell line, EL-4. The effect of CSA was to block the induction of active lymphokine mRNA, as assayed in an oocyte translation system. This selective inhibition of lymphokine mRNA suggests that CSA may be useful in the therapy of inflammatory, lymphokine-mediated disease states.
用伴刀豆球蛋白A诱导产生的三日龄T淋巴母细胞作为模型，研究致敏T细胞释放淋巴因子。这些母细胞对白介素2（IL-2）有反应，但不组成性产生这种或其他淋巴因子。经丝裂原再次刺激后，母细胞合成IL-2以及γ-干扰素、B细胞刺激因子和溶细胞分化因子。这种产生是由生物活性淋巴因子mRNA的诱导所致。环孢菌素A（CSA）是一种强效免疫抑制剂，强烈抑制经丝裂原再次刺激的T母细胞合成IL-2、γ-干扰素以及B细胞和CTL刺激因子。相比之下，CSA不阻断T母细胞的溶细胞活性，也不改变伴刀豆球蛋白A诱导的总体蛋白质合成。CSA还阻断佛波酯肉豆蔻酸酯刺激的胸腺瘤细胞系EL-4释放淋巴因子。如在卵母细胞翻译系统中所检测到的，CSA的作用是阻断活性淋巴因子mRNA的诱导。对淋巴因子mRNA的这种选择性抑制表明，CSA可能在治疗炎症性、淋巴因子介导的疾病状态中有用。
