Oral tolerance in the absence of naturally occurring Tregs.
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.
Mucida
Daniel
D
Program of Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.
Kutchukhidze
Nino
N
Erazo
Agustin
A
Russo
Momtchilo
M
Lafaille
Juan J
JJ
Curotto de Lafaille
Maria A
MA
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
D000941:Antigens; D018076:DNA, Complementary; D016212:Transforming Growth Factor beta; D010047:Ovalbumin