Elson C O, Ealding W
J Immunol. 1984 Jun;132(6):2736-41.
Cholera toxin (CT) has been found to be an extremely potent immunogen for mucosal IgA responses when administered via the intestine. This study has examined both mucosal and systemic immune responses after feeding CT and compared these responses with those obtained after feeding keyhole limpet hemocyanin (KLH), another protein that is strongly immunogenic in mice. Feeding CT to mice resulted not only in IgA antibody in intestinal secretions but also resulted in substantial plasma IgG and IgA antibody levels. Feeding KLH in much larger quantity resulted in little or no antibody response in intestinal secretions or plasma. Lymphoid cells from various tissues of mice fed CT were cultured in vitro for 10 days and the supernatant was tested for antibody to CT. Spontaneous antibody synthesis (no antigen added to cultures) was present in cultures of each cell type, but IgG anti-CT was found mainly in cultures of spleen and mesenteric lymph node cells and IgA anti-CT mainly in cultures of Peyer's patch and lamina propria cells. Peyer's patch cells cultured with CT as antigen synthesized both IgG and IgA anti-CT, suggesting that the antibody response to both isotypes originated in this site. Helper T cell activity for both IgA and IgG anti-CT was detected in spleens, mesenteric lymph nodes, and Peyer's patches. Lastly, when KLH and CT were fed to mice at the same time, an intestinal IgA anti-KLH and plasma IgG anti-KLH response was stimulated, a response pattern similar to that occurring to CT after CT was fed alone. We conclude that mucosal stimulation by CT generates both a systemic IgG and mucosal IgA response to this antigen, and that CT can cause a similar pattern of response to an unrelated protein antigen when both are administered into the intestine at the same time. The data favor the idea that both the IgG and IgA responses originate in GALT and then disseminate to other tissues. We propose that CT accomplishes these effects by altering the regulatory environment within GALT.
霍乱毒素（CT）经肠道给药时，已被发现是一种极其有效的诱导黏膜IgA应答的免疫原。本研究检测了喂食CT后的黏膜和全身免疫应答，并将这些应答与喂食血蓝蛋白（KLH）后的应答进行了比较，KLH是另一种在小鼠中具有强免疫原性的蛋白质。给小鼠喂食CT不仅导致肠道分泌物中出现IgA抗体，还导致血浆中IgG和IgA抗体水平显著升高。大量喂食KLH在肠道分泌物或血浆中几乎没有或没有引起抗体应答。将喂食CT的小鼠不同组织的淋巴细胞体外培养10天，并检测上清液中抗CT抗体。每种细胞类型的培养物中都存在自发抗体合成（培养物中未添加抗原），但IgG抗CT主要存在于脾脏和肠系膜淋巴结细胞的培养物中，而IgA抗CT主要存在于派尔集合淋巴结和固有层细胞的培养物中。用CT作为抗原培养的派尔集合淋巴结细胞合成了IgG和IgA抗CT，这表明对两种同种型的抗体应答都起源于该部位。在脾脏、肠系膜淋巴结和派尔集合淋巴结中检测到了针对IgA和IgG抗CT的辅助性T细胞活性。最后，当同时给小鼠喂食KLH和CT时，刺激了肠道IgA抗KLH和血浆IgG抗KLH应答，这种应答模式与单独喂食CT后对CT的应答模式相似。我们得出结论，CT的黏膜刺激产生了针对该抗原的全身IgG和黏膜IgA应答，并且当CT和无关蛋白质抗原同时经肠道给药时，CT可引起对该无关蛋白质抗原的类似应答模式。数据支持IgG和IgA应答均起源于肠道相关淋巴组织（GALT）然后扩散到其他组织的观点。我们提出CT通过改变GALT内的调节环境来实现这些效应。
