Systemic IL-2/anti-IL-2Ab complex combined with sublingual immunotherapy suppresses experimental food allergy in mice through induction of mucosal regulatory T cells.
BACKGROUND
Therapeutic tolerance restoration has been proven to modify food allergy in patients and animal models and although sublingual immunotherapy (SLIT) has showed promise, combined therapy may be necessary to achieve a strong and long-term tolerance.


AIMS
In this work, we combined SLIT with systemic administration of IL-2 associated with an anti-IL-2 monoclonal antibody (IL-2/anti-IL-2Ab complex or IL-2C) to reverse the IgE-mediated experimental allergy.


MATERIALS AND METHODS
Balb/c mice were sensitized with cholera toxin and milk proteins and orally challenged with allergen to elicit hypersensitivity reactions. Then, allergic mice were treated with a sublingual administration of very low amounts of milk proteins combined with intraperitoneal injection of low doses of IL-2C. The animals were next re-exposed to allergens and mucosal as well as systemic immunological parameters were assessed in vivo and in vitro.


RESULTS
The treatment reduced serum specific IgE, IL-5 secretion by spleen cells and increased IL-10 and TGF-β in the lamina propria of buccal and duodenal mucosa. We found an augmented frequency of IL-10-secreting CD4+ CD25+ Foxp3+ regulatory T cells (Treg) in the submaxilar lymph nodes and buccal lamina propria. Tregs were sorted, characterized and adoptively transferred to naïve mice, which were subsequently sensitized. No allergy was experienced in these mice and we encouragingly discovered a faster and more efficient tolerance induction with the combined therapy compared with SLIT.


CONCLUSION
The combination of two therapeutic strategies rendered Treg-mediated tolerance 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 it may represent a promising disease-modifying therapy for managing food allergy.
['Smaldini|P L|PL|', 'Trejo|F|F|', 'Cohen|J L|JL|', 'Piaggio|E|E|', 'Docena|G H|GH|0000-0002-0092-3169']
D000818:Animals D000911:Antibodies, Monoclonal D005512:Food Hypersensitivity D007376:Interleukin-2 D051379:Mice D008807:Mice, Inbred BALB C D009061:Mouth Mucosa D063729:Sublingual Immunotherapy D050378:T-Lymphocytes, Regulatory
IL-2 sublingual immunotherapy food allergy IgE mucosa Tregs gut