Oral tolerance induced by ovalbumin modulates the cytokine profile and increases the frequency of CD4+FoxP3+Helios+ Tregs expressing the GARP/LAP late-stage activation markers in antigen-stimulated cells of P.paulista wasp venom-sensitized mice.

Abstract

Background: Venom immunotherapy (VIT) successfully modulates immune responses to venom allergens. However, it may fail in multisensitized patients and cause severe adverse reactions. Bystander suppression mechanisms could enhance VIT efficacy by creating a tolerogenic microenvironment that induces modulatory effects in immune cells, suppressing allergic responses.

Objective: This study evaluated the immunomodulatory effect of an oral tolerance induction protocol to ovalbumin (OVA) in an experimental mouse model of allergen sensitization to Polybia paulista (P. paulista) wasp venom.

Methods: The humoral immune response was evaluated after the antigen challenge by quantification of specific Immunoglobulin E (sIgE) and mouse mast cell protease 1 (mMcpt1). The functional profiles of splenic dendritic cells and T cells stimulated in vitro with wasp venom allergens or OVA were also analyzed.

Results: We observed that oral tolerance induced to OVA modulated the humoral response of previously wasp venom-sensitized mice, reducing the mMcpt1 production but not altering the sIgE to venom allergens of P.paulista wasp. Regarding the cellular response, we observed an increase of tolerogenic DCs and an increased production of IFN-γ, TNF-α, IL-17A and IL-10 cytokines in the cells stimulated with wasp venom allergens. Moreover, there was an increase in the frequency of CD4⁺FoxP3⁺Helios⁺ Treg expressing GARP/LAP markers in comparison with their respective controls.

Conclusion: The results suggest that oral tolerance, induced by uncorrelated protein antigen, produces a regulatory immune profile in previously allergen-sensitized mice, which could be exploited to improve the safety and efficacy of AIT protocols, particularly for highly immunogenic allergens.