Taliaferro W H, Taliaferro L G
Proc Natl Acad Sci U S A. 1970 Aug;66(4):1036-43. doi: 10.1073/pnas.66.4.1036.
The effects of actinomycin D were studied on successive stages of the primary and secondary (anamnestic) anti-Forssman immunoglobulin hemolysin responses induced in rabbits by the antigen, sheep red blood cells. (Fully developed anamnestic reactivity was tested 1.5-2 months after the start of an untreated initial response.) The stages of both responses include induction by antigen, the latent period, the acute rise of hemolysin to peak titer, and the decline afterwards. This antibiotic modified both responses significantly in ways strikingly similar to those produced by large doses of x-rays. It was injected in a sublethal amount (0.08 mg/kg) at selected times before or after a test intravenous injection of 10(8.3) sheep erythrocytes/kg. Given within several days before the antigen, it delayed and depressed peak titer, whereas given during induction and the latent period, it delayed and enhanced peak titer. Given during the acute rise, its effect decreased, and given during the decline after peak titer, it only produced erratic slight rises in titer. It is suggested that delayed and depressed peak titers are associated with both known activities of sublethal doses of actinomycin D, i.e., cytotoxicity and inhibition of RNA synthesis, whereas enhanced peak titers are brought about by the presence of nucleic acid degradation products released by the cytotoxicity of actinomycin D at the critical time of active RNA synthesis in the latent period. Effects of actinomycin D differed quantitatively in the two responses. During the initial response, delayed depression was not apparent as soon and did not last as long, whereas delayed enhancement was more pronounced. In terms of the cells operating in the two responses, the data indicate that immunologically competent initial cells, as compared to memory cells, are more easily stimulated, are not injured as quickly, recover more rapidly, and overcompensate for the injury for a longer time. In addition, in untreated controls, recruitment of immunologically competent initial cells appears to be largely inhibited during induction of memory cells. Otherwise, decline of the secondary response would be less abrupt.
研究了放线菌素D对家兔由抗原（绵羊红细胞）诱导的初次和二次（回忆性）抗福斯曼免疫球蛋白溶血素反应连续阶段的影响。（在未处理的初次反应开始1.5 - 2个月后测试完全发育的回忆性反应性。）两种反应的阶段包括抗原诱导、潜伏期、溶血素急剧上升至峰值效价以及随后的下降。这种抗生素对两种反应都有显著改变，其方式与大剂量X射线产生的改变极为相似。在静脉注射10(8.3)个绵羊红细胞/千克进行测试之前或之后的选定时间，以亚致死量（0.08毫克/千克）注射该抗生素。在抗原注射前几天给予，它会延迟并降低峰值效价，而在诱导期和潜伏期给予时，它会延迟并提高峰值效价。在急剧上升期给予时，其效果减弱，在峰值效价后的下降期给予时，它只会使效价出现不稳定的轻微上升。有人认为，延迟和降低的峰值效价与亚致死剂量放线菌素D的两种已知活性有关，即细胞毒性和RNA合成抑制，而升高的峰值效价是由于在潜伏期活跃RNA合成的关键时期，放线菌素D的细胞毒性释放的核酸降解产物的存在所致。放线菌素D在两种反应中的作用在数量上有所不同。在初次反应期间，延迟性抑制没有那么快显现且持续时间没有那么长，而延迟性增强更为明显。就两种反应中起作用的细胞而言，数据表明，与记忆细胞相比，免疫活性初始细胞更容易被刺激，不会很快受到损伤，恢复得更快，并且在更长时间内对损伤进行过度补偿。此外，在未处理的对照中，在记忆细胞诱导期间，免疫活性初始细胞的募集似乎在很大程度上受到抑制。否则，二次反应的下降不会那么突然。
