Oral tolerance in the absence of naturally occurring Tregs
Daniel Mucida, … , Juan J. Lafaille, Maria A. Curotto de Lafaille
Daniel Mucida, … , Juan J. Lafaille, Maria A. Curotto de Lafaille
Published July 1, 2005
Citation Information: J Clin Invest. 2005;115(7):1923-1933. https://doi.org/10.1172/JCI24487.
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Research Article Immunology

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 CD4+CD25+Foxp3+CD45RBlow 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-β 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

Daniel Mucida, Nino Kutchukhidze, Agustin Erazo, Momtchilo Russo, Juan J. Lafaille, Maria A. Curotto de Lafaille

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Figure 7

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CD4+CD25+ T cells induced by oral tolerance or immunization suppress IgE...
CD4+CD25+ T cells induced by oral tolerance or immunization suppress IgE production in vivo. T/B monoclonal mice were administered OVA in drinking water and immunized with OVA-HA as represented in Figure 1A. Ten days after immunization, spleen and mLN cells were collected and pooled for the sorting of CD4+CD25+ and CD4+CD25– populations. (A and B) 5 × 105 CD4+CD25+ or CD4+CD25– from Tol T/B monoclonal mice cells were injected i.v. into BALB/c mice together with 5 × 105 OVA-specific naive CD4+ cells and 1 × 107 HA-specific naive B cells. One day after transfer, recipient mice were immunized i.p. with OVA-HA in alum. The figure shows total IgE and HA-specific IgG1 serum levels (bars) as well as the percentage of donor OVA-specific KJ1-26+ cells (triangles) 14 days after immunization. Results are expressed as mean ± SEM of 3–4 mice per group. Results in A and B correspond to 2 independent experiments. (C) CD4+CD25+ cells were purified from Tol and Imm groups 10 days after i.p. immunization and transferred to T/B monoclonal mice (5 × 105 cells/mouse). One day later, mice were immunized i.p. with OVA-HA in alum. The graphic shows serum IgE levels on day 15 after immunization. Results are expressed as mean ± SEM of 3 mice per group.