Bunjes D, Hardt C, Röllinghoff M, Wagner H
Eur J Immunol. 1981 Aug;11(8):657-61. doi: 10.1002/eji.1830110812.
The site of action of the immunosuppressive drug cyclosporin A in in vitro cytotoxic allograft responses has been localized. General cytotoxic effects of the drug on proliferating T cells became apparent at concentrations of 500-1000 ng/ml, while selective effects were observed at concentrations of 10-100 ng/ml. The selective effects included a blockade of interleukin 2 release from activated T helper cells on the one hand and inhibition of interleukin 1 release from splenic adherent cells on the other. While cyclosporin A did not interfere with the intracellular events required for the activation and subsequent clonal expansion of alloreactive T cells, the lack of interleukin 1 and interleukin 2 induced by cyclosporin A results in an inability of T responder cells to mount cytotoxic allograft responses in vitro.
免疫抑制药物环孢素A在体外细胞毒性同种异体移植反应中的作用位点已被定位。该药物对增殖T细胞的一般细胞毒性作用在浓度为500 - 1000纳克/毫升时变得明显,而在浓度为10 - 100纳克/毫升时观察到选择性作用。选择性作用一方面包括阻断活化的T辅助细胞释放白细胞介素2,另一方面包括抑制脾黏附细胞释放白细胞介素1。虽然环孢素A不干扰同种反应性T细胞活化及随后克隆扩增所需的细胞内事件,但环孢素A诱导的白细胞介素1和白细胞介素2的缺乏导致T反应细胞在体外无法引发细胞毒性同种异体移植反应。