Ruedl C, Rieser C, Kofler N, Wick G, Wolf H
Institute for General and Experimental Pathology, Medical School, University of Innsbruck, Austria.
Vaccine. 1996 Jun;14(8):792-8. doi: 10.1016/0264-410x(95)00231-o.
Cholera toxin (CT) and Escherichia coli heat-labile enterotoxin (LT) are the strongest mucosal immunogens identified to date and are also good adjuvants when given orally together in combination with unrelated antigens. We used these potent immunogens to monitor local and systemic immune responses following oral immunization of BALB/c mice, and compared their action on the following: (a) immunoglobulin production rates (IgG, IgM and IgA) in mucosal inductive (Peyer's patches-PPs), effector (intestinal lamina propria-LP, respiratory tract) and systemic (spleen) sites; (b) analysis of systemic antigen-specific antibodies (IgG subclasses, IgA and IgE); (c) time monitoring of fecal anti-CT and anti-LT antibodies, and (d) in vivo relevance of interleukin-6 (IL-6) to mucosal responses. Both mucosal immunogens elicited specific antibody responses (IgA, IgG) not only in the gastrointestinal tract (PP's and intestinal LP), but also in the respiratory tract and spleens of orally immunized mice. These mucosal responses were accompained by elevated secretion of IL-6 in all investigated tissues, indicating involvement of this cytokine in B-cell maturation processes. Furthermore, oral immunization with CT and LT induced elevated serum titers of IgG1 followed by IgG2a, IgG2b, IgG3 and IgA, while high antigen-specific IgA and IgG1 responses were found in fecal extracts. These findings illustrate the action of orally administered CT and LT, respectively, on several humoral and cellular immune responses not only at the gastrointestinal tract, the application site, but also in distant mucosal effector sites such as the respiratory tract. These data suggest the potential use of these mucosal adjuvants in oral immunization strategies to improve the local immune response in remote mucosal tissues, in accordance with the concept of a common mucosa-associated immune system.
霍乱毒素（CT）和大肠杆菌不耐热肠毒素（LT）是迄今为止发现的最强的黏膜免疫原，当与不相关抗原一起口服时，它们也是良好的佐剂。我们使用这些强效免疫原监测BALB/c小鼠口服免疫后的局部和全身免疫反应，并比较它们在以下方面的作用：（a）黏膜诱导部位（派尔集合淋巴结-PPs）、效应部位（肠道固有层-LP、呼吸道）和全身部位（脾脏）的免疫球蛋白产生率（IgG、IgM和IgA）；（b）全身抗原特异性抗体（IgG亚类、IgA和IgE）的分析；（c）粪便抗CT和抗LT抗体的时间监测，以及（d）白细胞介素-6（IL-6）与黏膜反应的体内相关性。两种黏膜免疫原不仅在口服免疫小鼠的胃肠道（PPs和肠道LP），而且在呼吸道和脾脏中都引发了特异性抗体反应（IgA、IgG）。这些黏膜反应伴随着所有研究组织中IL-6分泌的增加，表明该细胞因子参与了B细胞成熟过程。此外，用CT和LT进行口服免疫诱导血清中IgG1滴度升高，随后是IgG2a、IgG2b、IgG3和IgA升高，而在粪便提取物中发现了高抗原特异性IgA和IgG1反应。这些发现分别说明了口服CT和LT不仅对胃肠道（应用部位），而且对远处黏膜效应部位如呼吸道的几种体液和细胞免疫反应的作用。这些数据表明，根据共同黏膜相关免疫系统的概念，这些黏膜佐剂在口服免疫策略中具有潜在用途，可改善远端黏膜组织中的局部免疫反应。
