title: Induction of immunological tolerance by oral, but not intravenous and intraportal, administration of ovalbumin and the difference between young and old mice.
abstract: BACKGROUND
  Induction of immunological tolerance is dependent on the route of antigenic administration, the dose of an antigen and the age of animals.
  
  
  OBJECTIVE
  We investigated the effect of age on the tolerance induction in mice by administration of antigen through different routes and at different doses.
  
  
  METHODS
  Young and old BDF1 mice were orally, intraportally or intravenously administrated with a low or a high dose of ovalbumin (OVA). Then, delayed-type hypersensitivity (DTH) responses and serum anti-OVA antibody levels were assessed after systemic immunization of OVA with alum after appropriate intervals.
  
  
  RESULTS
  In the young mice, oral administration of OVA suppressed DTH response and anti-OVA IgG1, IgG2b, IgM and IgE level in a dose-dependent manner. In the old mice, however, the suppression of IgG1 and IgE levels was induced by oral administration of a low dose of OVA, but no suppression by a high dose. On the other hand, intraportal or intravenous injection of OVA did not suppress DTH response and enhanced anti-OVA antibody levels in a dose-dependent manner in both young and old mice. Production of anti-OVA IgG2a antibody after systemic injection of OVA was detected in the mice, which had been treated with intraportal or intravenous injection of OVA, but not detected in the mice, which had been treated with oral administration of OVA. On the contrary, suppression of anti-OVA IgE antibody was observed only in the mice, which had been treated with oral administration of OVA.
  
  
  CONCLUSIONS
  The oral administration of OVA, neither intravenous nor intraportal, induced immunological tolerance to OVA. An adequate dose of OVA for the tolerance induction and the suppression of antibody production are different between young and old mice. The suppression of IgE antibody was observed only by oral administration of OVA, much obviously in young mice than in the old. The results also indicated that the antigen processing in the liver did not play a major role in the induction of oral tolerance to OVA.
authors.affiliation: Department of Microbiology and Immunology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan. awaka@nms.ac.jp
authors.forename: A
authors.initials: A
authors.lastname: Wakabayashi
authors.forename: M
authors.initials: M
authors.lastname: Utsuyama
authors.forename: T
authors.initials: T
authors.lastname: Hosoda
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: H
authors.initials: H
authors.lastname: Takahashi
authors.forename: K
authors.initials: K
authors.lastname: Hirokawa
mesh_terms: D000284:Administration, Oral; D000375:Aging / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation; D000941:Antigens; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D006968:Hypersensitivity, Delayed / Q000453:epidemiology / Q000276:immunology*; D007108:Immune Tolerance; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology; D011168:Portal System / Q000502:physiology; D011897:Random Allocation
chemical_list: D000941:Antigens; D010047:Ovalbumin