Interleukin-2/anti-interleukin-2 antibody complexes expand T regulatory cells and protect against allergen-induced airway hyperreactivity (HYP7P.256)

Abstract

Abstract T-cells play a key role in the development and maintenance of allergic diseases and thus represent a promising target for therapeutic interventions. Evidence from SIT studies suggest that regulatory T-cells (Treg) might counterbalance the Th2-biased immune response. We here created double transgenic (tg) allergy mice expressing a human TCR specific for the major mugwort (Artemisia vulgaris) pollen allergen Art v 1 and HLA-DR1 to study the response to the aero-allergen in vivo. After allergen-specific sensitization, only double tg allergy mice, but not single tg or wt control mice showed enhanced airway-hyperreactivity (AHR) upon challenge, which was associated with airway and lung inflammation. Significantly, treatment of allergy mice with three daily i.p. injections of IL-2/anti-IL-2 mAb complexes induced a 6-fold increase of CD25+Foxp3+ Treg among CD3+CD4+T-cells in peripheral blood (17.9±6.2% versus 3.1±1.4%) compared to a 8-fold increase of CD39+ and KLRG1+ Treg subsets, respectively (17.2±7.9% versus 2.1±1.5%; 1.6±0.2% versus 0.2±0.2%). Furthermore, expansion of Treg by IL-2/anti-IL-2 mAb complexes before sensitization prevented mice from allergen-induced AHR upon challenge and significantly reduced Art v 1-specific serum IgE, when compared to sham-treated mice. Such in vivo expanded Treg might have similar effects in therapeutic settings. In summary, expansion of Treg by IL-2/anti-IL-2 mAb complexes seems to be a promising strategy to interfere with allergic diseases.