Pierce N F
J Exp Med. 1978 Jul 1;148(1):195-206. doi: 10.1084/jem.148.1.195.
This report describes studies of the mucosal antitoxic response in rats after enteric administration of several forms of cholera toxin or toxoid, proteins which differ primarily in their ability to bind to cell membranes and activate cellular adenyl cyclase. These two characteristics appeared to markedly enhance the local primary response to these antigens. A single dose of toxoid lacking these features was ineffective in local priming even though it was absorbed and induced a systemic immune response. Single dose mucosal priming occurred only with preparations which bind to cell membranes and was enhanced by those which also activate cellular adenyl cyclase. In contrast, single-dose mucosal boosting was best accomplished by materials with these properties but was also seen with a toxoid lacking both of these functions. The property of membrane binding appears to be most advantageous in mucosal priming, perhaps by increasing effective trapping of absorbed antigen in unprimed mucosal lymphoid tissue, whereas the ability to activate adenyl cyclase appears to enhance primary and secondary type responses about equally. Combinations of crude toxoid and toxin were also more effective in mucosal priming than purified materials, a finding which is unexplained. A single dose of this combination induced mucosal priming which was fully developed in 2 wk, undiminished after 4 too, and only modestly diminished after 8 mo, thus demonstrating relatively prolonged memory in the IgA mucosal immune system. Effective two-dose local immunizing regimens were developed, and it was shown that there was no correlation between the mucosal and systemic secondary antitoxin responses provoked by these regimens.
本报告描述了大鼠经肠道给予几种形式的霍乱毒素或类毒素后黏膜抗毒反应的研究，这些蛋白质主要在与细胞膜结合及激活细胞腺苷酸环化酶的能力方面存在差异。这两个特性似乎显著增强了对这些抗原的局部初次反应。单剂量缺乏这些特性的类毒素在局部启动方面无效，尽管它被吸收并诱导了全身免疫反应。单剂量黏膜启动仅发生在与细胞膜结合的制剂中，并且会被那些还能激活细胞腺苷酸环化酶的制剂增强。相比之下，单剂量黏膜加强免疫最好通过具有这些特性的物质来完成，但也可见于缺乏这两种功能的类毒素。膜结合特性在黏膜启动中似乎最具优势，可能是通过增加未启动的黏膜淋巴组织中吸收抗原的有效捕获，而激活腺苷酸环化酶的能力似乎对初次和二次反应的增强作用大致相同。粗制类毒素和毒素的组合在黏膜启动方面也比纯化物质更有效，这一发现尚无合理解释。单剂量的这种组合诱导的黏膜启动在2周时完全形成，4周后未减弱，8个月后仅略有减弱，从而证明了IgA黏膜免疫系统中相对持久的记忆。开发了有效的两剂量局部免疫方案，结果表明这些方案引发的黏膜和全身二次抗毒素反应之间没有相关性。
