ADOPTIVE TRANSFER OF REGULATORY T CELLS EFFECTIVELY SUPPRESSED ALLERGIC REACTIONS IN A MOUSE MODEL OF FOOD ALLERGY

SMALDINI PAOLA L; ORSINI DELGADO, M LUCÍA; FOSSATI, CARLOS A; DOCENA, GUILLERMO H

Buzioa

Congreso; XXXIX Congress of the Brazilian Society of Immunology; 2014

Sociedad Brasilera de Inmunologia

Introduction: Food allergy is an immune-mediated adverse reaction to food and its prevalence has increased worldwide. Deficient suppression of T cell response to allergen by CD4+CD25+ regulatory T cells has been observed in patients with allergic disease. We aimed to assess if adoptive transfer of induced-Treg could restore tolerance and subsequently alleviate food allergy in a mouse model. Methods and Results: Balb/c mice were orally given CMP (CMPprev) prior to oral sensitization with CMP and cholera toxin (prevention), or after sensitization (desensitization) (CMPdes). Mice were orally challenged with CMP and the immune response was evaluated with in vivo (clinical score and cutaneous tests) and in vitro assays (serum specific IgE, IgG1, IgG2a; IL-5, IL-13, IFN-γ, IL-10 and TGF-β secretion by spleen cells, and analysis of Treg cells in the intestinal mucosa). In vitro natural differentiated Treg (nTreg) and in vivo MLN induced-Treg (iTreg) cells were intravenously transferred to naïve mice before sensitization. We found that symptoms were controlled with oral administration of CMP, with a concomitant negative skin test. Accordingly, serum specific IgE and IgG1 were abrogated and a substantial reduction in the secretion of IL-5 and IL-13 by stimulated spleen cells from sensitized mice was observed. Importantly, we found that IL-10 and TGF-β were induced with treatment along with an induction of CD4+CD25+FoxP3+ cells (1,02±0,3% vs 10,5±0,5% CMPdes; 4,30±0,2% CMPprev) and IL-10- and TGF-β-producing regulatory T cells (Tregs) in the lamina propria and in MLN. Transfer of differentiated Treg from spleen cells (nTreg) or MLN induced regulatory cells (iTreg) significantly attenuated CMP-induced allergic inflammation, alleviated clinical signs (average score to sensitized mice=3; iTreg=1 and nTreg=1,5), reduced levels of serum IgE and depicted negative skin test. Conclusion: We concluded that in vitro and in vivo-induced CD4+CD25+Foxp3+ Treg controlled the allergic response. Oral allergen immunotherapy may enhance the development of Treg to control the allergic inflammation.