Importance of gastrointestinal ingestion and macromolecular antigens in the vein for oral tolerance induction
Importance of gastrointestinal ingestion and macromolecular antigens in the vein for oral tolerance induction
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DOI：
10.1111/j.1365-2567.2006.02418.x
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发表时间：
2006-10
期刊：
影响因子：
6.4
通讯作者：
A. Wakabayashi;Y. Kumagai;E. Watari;Masumi Shimizu;M. Utsuyama;K. Hirokawa;Hidemi Takahashi
中科院分区：
文献类型：
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作者：
A. Wakabayashi;Y. Kumagai;E. Watari;Masumi Shimizu;M. Utsuyama;K. Hirokawa;Hidemi Takahashi
口服一定剂量的抗原，一般可诱导针对同一抗原的免疫耐受。在这项研究中，我们显示了卵清蛋白（OVA）抗原的时间出现在小鼠门静脉和外周血后，口服给药的OVA。此外，我们检测到45 000 MW的OVA在小鼠血清中的口服给药后30分钟。基于这一观察结果，我们研究了将完整的OVA注射到门静脉或外周静脉中是否诱导针对OVA的免疫耐受。我们发现，静脉注射完整的OVA不会诱导免疫耐受，但会增强某些亚类中的OVA特异性抗体产生，这表明通过胃肠道的OVA抗原而不是完整的OVA可能有助于建立对OVA的免疫耐受。因此，我们研究了在胃肠道中消化完整的OVA对诱导口服耐受性的影响。当小鼠经口给药或注射到胃、十二指肠、回肠或结肠等各种胃肠道器官中并用完整的OVA加强时，与经口给药的小鼠相比，注射到回肠或结肠中的小鼠中的OVA特异性抗体产生和迟发型超敏反应（DTH）显著增强。这些结果表明，尽管在耐受小鼠血清中经口给予OVA后检测到大分子OVA抗原，但注射完整的OVA不能诱导耐受。因此，在胃肠道和摄入中对大分子OVA进行一些修饰可能是口服耐受诱导所必需的。
Oral administration of a certain dose of antigen can generally induce immunological tolerance against the same antigen. In this study, we showed the temporal appearance of ovalbumin (OVA) antigens in both portal and peripheral blood of mice after the oral administration of OVA. Furthermore, we detected 45 000 MW OVA in mouse serum 30 min after the oral administration of OVA. Based on this observation, we examined whether the injection of intact OVA into the portal or peripheral vein induces immunological tolerance against OVA. We found that the intravenous injection of intact OVA did not induce immunological tolerance but rather enhanced OVA‐specific antibody production in some subclasses, suggesting that OVA antigens via the gastrointestinal tract but not intact OVA may contribute to establish immunological tolerance against OVA. Therefore, we examined the effects of digesting intact OVA in the gastrointestinal tract on the induction of oral tolerance. When mice were orally administered or injected into various gastrointestinal organs, such as the stomach, duodenum, ileum, or colon and boosted with intact OVA, OVA‐specific antibody production and delayed‐type hypersensitivity (DTH) response were significantly enhanced in mice injected into the ileum or colon, compared with orally administered mice. These results suggest that although macromolecular OVA antigens are detected after oral administration of OVA in tolerant‐mouse serum, injection of intact OVA cannot contribute to tolerance induction. Therefore, some modification of macromolecular OVA in the gastrointestinal tract and ingestion may be essential for oral tolerance induction.