title: Oral tolerance in the absence of naturally occurring Tregs.
abstract: Mucosal tolerance prevents pathological reactions against environmental and food antigens, and its failure results in exacerbated inflammation typical of allergies and asthma. One of the proposed mechanisms of oral tolerance is the induction of Tregs. Using a mouse model of hyper-IgE and asthma, we found that oral tolerance could be effectively induced in the absence of naturally occurring thymus-derived Tregs. Oral antigen administration prior to i.p. immunization prevented effector/memory Th2 cell development, germinal center formation, class switching to IgE, and lung inflammation. Oral exposure to antigen induced development of antigen-specific CD4CD25Foxp3CD45RB cells that were anergic and displayed suppressive activity in vivo and in vitro. Oral tolerance to the Th2 allergic response was in large part dependent on TGF-beta and independent of IL-10. Interestingly, Tregs were also induced by single i.p. immunization with antigen and adjuvant. However, unlike oral administration of antigen, which induced Tregs but not effector T cells, i.p. immunization led to the simultaneous induction of Tregs and effector Th2 cells displaying the same antigen specificity.
authors.affiliation: Program of Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mucida
authors.forename: Nino
authors.initials: N
authors.lastname: Kutchukhidze
authors.forename: Agustin
authors.initials: A
authors.lastname: Erazo
authors.forename: Momtchilo
authors.initials: M
authors.lastname: Russo
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Lafaille
authors.forename: Maria A
authors.initials: MA
authors.lastname: Curotto de Lafaille
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D001249:Asthma / Q000276:immunology / Q000473:pathology; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D007274:Injections, Intraperitoneal; D007589:Job Syndrome / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009500:Neutralization Tests; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors
chemical_list: D000941:Antigens; D018076:DNA, Complementary; D016212:Transforming Growth Factor beta; D010047:Ovalbumin