Systemic IL-2/anti-IL-2Ab complex combined with sublingual immunotherapy suppresses experimental food allergy in mice through induction of mucosal regulatory T cells

COHEN, JOSÉ L; TREJO, FERNANDO; SMALDINI, PAOLA L.; DOCENA, GUILLERMO H.; PIAGGIO, ELIANE

ALLERGY

WILEY-BLACKWELL PUBLISHING, INC

Año: 2018

0105-4538

Therapeutic tolerance restoration has been proven to modify food allergy in patients andanimal models and although sublingual immunotherapy (SLIT) has showed promise,combined therapy may be necessary to achieve a strong and long-term tolerance. In thiswork, we combined SLIT with systemic administration of IL-2 associated with an anti-IL-2monoclonal antibody (IL-2/anti-IL-2Ab complex or IL-2C) to reverse the IgE-mediatedexperimental allergy.Balb/c mice were sensitized with cholera toxin and milk proteins and orally challenged withallergen to elicit hypersensitivity reactions. Then, allergic mice were treated with a sublingualadministration of very low amounts of milk proteins combined with intraperitoneal injectionof low doses of IL-2C. The animals were next re-exposed to allergens and mucosal as well assystemic immunological parameters were assessed in vivo and in vitro.The treatment reduced serum specific IgE, IL-5 secretion by spleen cells and increased IL-10and TGF-β in the lamina propria of buccal and duodenal mucosae. We found an augmentedfrequency of IL-10-secreting CD4+CD25+Foxp3+ regulatory T cells (Treg) in the submaxilarlymph nodes and buccal lamina propria. Tregs were sorted, characterized and adoptivelytransferred to naïve mice, which were subsequently sensitized. No allergy was experienced inthese mice and we encouragingly discovered a faster and more efficient tolerance inductionwith the combined therapy compared with SLIT.In conclusion, the combination of two therapeutic strategies rendered Treg-mediatedtolerance more efficient compared to individual treatments and reversed the established IgE-mediated food allergy. This approach highlights the ability of IL-2C to expand Tregs, and itmay represent a promising disease-modifying therapy for managing food allergy.