Ryffel B, Feurer C, Heuberger B, Borel J F
Immunobiology. 1982 Dec;163(5):470-83. doi: 10.1016/S0171-2985(82)80061-2.
The immunosuppressive effect of CS-A was first studied in the assay for local GvHR. 3 X 10(6) viable spleen cells from LEW rats were injected into one foot pad of LEW X BN hybrids and both PLN were weighed 7 days later. Treatment of the recipients with 3 doses of 50 mg/kg/day of CS-A suppressed this local GvHR. The effect was more pronounced when treatment started at the time of cell transfer rather than a few days before peak response. In vitro incubation of the cellular inoculum with CS-A also prevented local GvHR. Histology of the PLN confirmed the quantitative results expressed by the PLN index. CS-A was further investigated in the EAE model in LEW rats. It protected rats sensitised with spinal cord emulsified in complete Freund's adjuvant for as long as they were treated with CS-A. Treatment delayed until after the appearance of EAE also markedly improved their condition. Oral treatment of recipients with 50 mg/kg/day CS-A prevented the development of adoptive EAE following the transfer of lymphoid cells conditioned in vitro. The presence of 0.1-1.0 microgram CS-A in the medium of the sensitised lymphoid cells also inhibited the adoptive transfer of EAE. Finally, if the cells for the adoptive transfer were derived from CS-A-treated sensitised donors, they failed to induce EAE. Histological examination supported the symptomatic findings.
环孢素A(CS - A)的免疫抑制作用最初是在局部移植物抗宿主反应(GvHR)试验中进行研究的。将3×10⁶个来自LEW大鼠的活脾细胞注射到LEW×BN杂交种的一个足垫中,7天后称量双侧腹股沟淋巴结(PLN)的重量。接受者用3剂50mg/kg/天的CS - A进行治疗可抑制这种局部GvHR。当在细胞转移时而非在反应高峰期前几天开始治疗时,这种作用更为明显。将细胞接种物与CS - A进行体外孵育也可预防局部GvHR。PLN的组织学检查证实了由PLN指数所表达的定量结果。在LEW大鼠的实验性自身免疫性脑脊髓炎(EAE)模型中对CS - A进行了进一步研究。只要用CS - A对大鼠进行治疗,它就能保护用完全弗氏佐剂乳化的脊髓致敏的大鼠。治疗延迟到EAE出现后也能显著改善它们的状况。接受者口服50mg/kg/天的CS - A可预防在体外预处理的淋巴细胞转移后发生的过继性EAE。在致敏淋巴细胞培养基中存在0.1 - 1.0微克的CS - A也可抑制EAE的过继性转移。最后,如果用于过继性转移的细胞来自经CS - A处理的致敏供体,则它们不能诱导EAE。组织学检查支持了症状学发现。