title: Importance of gastrointestinal ingestion and macromolecular antigens in the vein for oral tolerance induction.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Nippon Medical School, Tokyo, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Wakabayashi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kumagai
authors.forename: Eiji
authors.initials: E
authors.lastname: Watari
authors.forename: Masumi
authors.initials: M
authors.lastname: Shimizu
authors.forename: Masanori
authors.initials: M
authors.lastname: Utsuyama
authors.forename: Katsuiku
authors.initials: K
authors.lastname: Hirokawa
authors.forename: Hidemi
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000276:Adjuvants, Immunologic; D000284:Administration, Oral; D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000097:blood / Q000276:immunology; D002772:Cholera Toxin / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D041981:Gastrointestinal Tract / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D007136:Immunoglobulins / Q000096:biosynthesis; D007275:Injections, Intravenous; D046911:Macromolecular Substances / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D010047:Ovalbumin / Q000008:administration & dosage* / Q000097:blood / Q000276:immunology; D011169:Portal Vein
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D007136:Immunoglobulins; D046911:Macromolecular Substances; D010047:Ovalbumin; D002772:Cholera Toxin