W109 - IL-2 Mutein Prevents the Development of Allergic Asthma

Abstract Text: Allergic asthma is a chronic inflammatory disease characterized by an aberrant type 2 immune response to aeroallergens. Type 2 cell-mediated responses drive allergic asthma due to an imbalance of allergen-specific effector and regulatory cell responses. Regulatory T cells (Tregs) are potent suppressors of inflammation and are attractive targets to treat allergic asthma. Interleukin-2 (IL-2) is essential for Treg function and IL-2 muteins, such as Fc.mut24, have been engineered to increase Treg selectivity and half-life. We hypothesized that targeting Tregs with IL-2-Fc.mut24 could tip the balance and lead to suppression of allergen-induced type 2 airway inflammation.

To assess this hypothesis, Fc.mut24 was given s.c. to C57BL/6 mice 3 days prior to sensitization with intranasal (i.n.) house dust mite (HDM) followed by i.n. HDM challenges on days 7–11 and harvested on day 15. Fc.mut24 treatment prevented the development of allergen-specific Th2 cells in the draining mediastinal lymph node and lung and prevented allergic airway inflammation and airway hyperreactivity. Fc.mut24 treatment prior to HDM sensitization had a long-term effect, as treated mice did not develop a Th2 cell recall response and lung inflammation following allergen rechallenge on day 42. In contrast, mice that first received Fc.mut24 in the memory phase - after HDM sensitization and challenge - did not suppress the Th2 cell recall response and developed airway inflammation following allergen rechallenge.

In conclusion, Fc.mut24 prevented the development of allergic airway inflammation, but once allergen-specific Th2 cell responses are established, Fc.mut24 treatment was unable to suppress allergen-induced allergic airway inflammation.