Bianchi A T, Zwart R J, Van der Heijden P J
Department of Immunology, Central Veterinary Institute, Lelystad, The Netherlands.
Reg Immunol. 1990;3(3):131-8.
We induced ovalbumin (OA)-specific antibody responses in the murine small intestine and quantitated the responses by counting ovalbumin-specific antibody-containing cells (OACC) in the intestinal lamina propria, and by measuring anti-OA Ig titers in intestinal secretions. OA is a "weak" mucosal antigen and we could only induce intestinal anti-OA responses by intraperitoneal, primary injection of OA in water-in-oil emulsion and a mucosal booster with OA. Double staining of OACC for OA- and isotype-specificity demonstrated that 95% of all mucosal (intestinal) OACC produced IgA, whereas 95% of all systemic (splenic) OACC produced IgG. The intestinal anti-OA response could be stimulated by addition of cholera toxin (CT) or cholera toxin B-subunit (CTB) during the mucosal booster immunization. The stimulatory effect of CT did not depend on covalent coupling of CT and OA, while the stimulatory effect of CTB required covalent coupling of CTB with OA. Mucosal (intraduodenal) application of OA as such does not prime for a mucosal and systemic OACC response but induces tolerance. We demonstrated that coupling of OA with CT or CTB could overcome the inability of mucosal application of OA to prime for a mucosal OACC response. Although CT proved to be much more effective than CTB in stimulation of mucosal immune responses and possibly in prevention of tolerance induction, our results indicate that CTB is a useful (and safer) alternative.
我们在小鼠小肠中诱导了卵清蛋白（OA）特异性抗体反应，并通过计数肠固有层中含卵清蛋白特异性抗体的细胞（OACC）以及测量肠分泌物中的抗OA Ig滴度来定量这些反应。OA是一种“弱”黏膜抗原，我们只能通过腹腔内初次注射油包水乳剂中的OA以及用OA进行黏膜加强免疫来诱导肠道抗OA反应。对OACC进行OA和同种型特异性的双重染色表明，所有黏膜（肠道）OACC中有95%产生IgA，而所有全身（脾脏）OACC中有95%产生IgG。在黏膜加强免疫期间添加霍乱毒素（CT）或霍乱毒素B亚单位（CTB）可刺激肠道抗OA反应。CT的刺激作用不依赖于CT与OA的共价偶联，而CTB的刺激作用需要CTB与OA共价偶联。单纯黏膜（十二指肠内）应用OA不会引发黏膜和全身OACC反应，反而会诱导耐受。我们证明，OA与CT或CTB偶联可以克服黏膜应用OA无法引发黏膜OACC反应的问题。尽管CT在刺激黏膜免疫反应以及可能预防耐受诱导方面比CTB有效得多，但我们的结果表明CTB是一种有用（且更安全）的替代物。
