Engineering a safe monoclonal anti-human IL-2 that is effective in a murine model of food allergy and asthma.

ABSTRACT

BACKGROUND: Regulatory T cells (Tregs) are known to protect against allergies. Moreover, the decrease in the frequency and efficiency of Tregs amplifies allergic symptoms. AIM: This study investigated whether expanding Tregs in vivo with an IL-2/IL-2 antibody complex could be safe, well tolerated and efficient in a therapeutic setting in allergies. METHODS: We produced an anti-IL-2 antibody (1C6) and demonstrated that when it is complexed to human IL-2, it increases IL-2 efficiency to induce Tregs in vivo without any detectable side effects. Furthermore, the IL-2/1C6 complex induces an increase in Helios expression by Tregs, suggesting that it not only elevated Treg numbers but also boosted their functions. Using mouse models of house-dust-mite-induced airway inflammation and wheat-gliadin-induced food allergies, we investigated the therapeutic potential of the IL-2/1C6 complex in allergies. RESULTS: IL-2/1C6 treatment significantly reduced allergic symptoms, specific IgE production, the adaptive immune response and tissue damage. Interestingly, IL-2/1C6 treatment modulated innate lymphoid cells by increasing ILC2s in asthma and decreasing ILC3s in food allergies. CONCLUSION: In conclusion,complexed IL-2/anti-IL-2 may restore Treg numbers and function in respiratory and food allergies, thereby improving allergic markers and symptoms. Our IL-2/anti-IL-2 complex offers new hope for reestablishing immune tolerance in patients with allergies.