Regulatory T Cells Control Type I Food Allergy to Beta-Lactoglobulin in Mice

Abstract

Background: Regulatory T cells contribute to peripheral immune tolerance, yet their ability to control immediate-type hypersensitivity (ITH) reactions involved in IgE-mediated food allergy is still poorly documented. Objectives: We investigated in mice whether CD4+CD25+ regulatory T cells could control ITH to β-lactoglobulin (BLG), a major allergen in cow’s milk. Methods: C3H/HeOuJ mice were sensitized by repeated oral gavage with BLG plus cholera toxin as adjuvant and orally challenged with BLG alone to elicit allergic symptoms. Mice were treated with the anti-CD25 mAb (PC61) before sensitization. Oral sensitization (afferent phase of ITH) was assessed by production of BLG-specific serum antibodies and Th1/Th2-type cytokines by specific CD4+ T cells in mesenteric lymph nodes. ITH was elicited by oral BLG challenge (efferent phase of ITH) and we monitored symptom scores, numbers and function of intestinal mast cells and serum level of the mucosal mast cell protease mMCP-1. Results: Upon oral BLG challenge, orally sensitized mice developed only mild clinical signs. Anti-CD25 mAb-treated mice exhibited enhancement of both BLG-specific CD4+ T cell priming with IL-4, IL-5, IL-13 and IFN-γ production and total IgE, and BLG-specific IgE, IgG1 and IgG2a in serum. Anti-CD25 mAb treatment caused more severe symptoms upon BLG challenge, which correlated with enhanced serum levels of the mucosal mast cell protease mMCP-1. Conclusions: These data document that constitutive CD4+CD25+ regulatory T cells alleviate clinical signs of ITH to dietary BLG by modulating the priming of BLG-specific T and B cell responses during oral sensitization and enhancing mast cell degranulation.

The regulatory T cells induction by epicutaneous immunotherapy is sustained and mediates long‐term protection from eosinophilic disorders in peanut‐sensitized mice

“…In a model of cow's milk allergy in mice, Kanjaraw et al. also observed that the depletion of CD25 + cells before immunization enhanced BLG‐specific CD4 + T cells and blood sIgE levels, which caused more severe symptoms upon BLG challenge . In our model, no difference was observed between naïve and sensitized mice in the frequency of Tregs.…”

Regulatory CD4+Foxp3+ T Cells Control the Severity of Anaphylaxis

“…FACS analysis in lymphoid organs showed that anti-CD25 mAb treatment resulted in >90% reduction of CD4 + CD25 + Treg frequency with concomitant increase in the percentage of Foxp3 + CD25 - T cells ( not shown ), indicative of a down-regulation of the CD25 molecule previously described to render Treg functionally inactive [22,28]. Anti-CD4 mAb-treated mice showed nearly complete (>99%) depletion of CD4 + T cells ( not shown ).…”

“…Thus, evidence that Foxp3 + Treg can control the symptomatic effector phase of immediate-type hypersensitivity and attenuate anaphylaxis remains scarce [21]. In this respect, we recently documented that anti-CD25 mAb injection before oral sensitization with a food allergen, enhanced both the priming of allergen-specific T and B cells and the severity of immediate-hypersensitivity symptoms after oral challenge [22]. Importantly, when the anti-CD25 mAb was injected just before challenge, we observed enhanced serum levels of mMCP1 [22] and more numerous degranulated intestinal MC (D. Kaiserlian, unpublished data ), suggesting a role for Treg on tissue MC cell degranulation during the symptomatic phase of anaphylaxis.…”

Molecular mechanisms of IgE mediated food allergy

“…A mutation of FoxP3 in children has been found to induce high Th2 responses as well as high IgE levels which indicate that the higher the level of Treg cells, the lower the chance of food allergy [55]. The constitutive CD4+CD25+ regulatory T cells alleviate clinical signs of immediate type hypersensitivity to dietary food allergen by modulating the priming of allergen-specific T and B cell responses during oral sensitization and enhancing mast cell degranulation [56].…”