Der p 1-specific regulatory T-cell response during house dust mite allergen immunotherapy

BackgroundAllergen-specific immunotherapy (AIT) is the only available treatment for allergic diseases that can induce specific immune tolerance to allergens. The key mechanisms involved in this process include changes in allergen-specific regulatory T (Treg) cells. MethodsWe studied 25 allergic rhinitis patients undergoing subcutaneous house dust mite-specific immunotherapy. Peripheral blood mononuclear cells were studied before and after 10, 30weeks, and 3years of AIT. Der p 1-specific T regulatory cell responses were investigated by characterization of Der p 1-MHC class II tetramer-positive cells and correlated with nasal symptom score. ResultsTwelve of 25 AIT patients matched with their MHC class II expression to the Der p 1 peptide-MHC class II tetramers. A significant increase in the numbers of Der p 1-specific FOXP3(+)Helios(+)CD25(+)CD127(-) Treg cells after 30weeks was observed, which slightly decreased after 3years of AIT. In contrast, Der p 1-specific immunoglobulin-like transcript 3 (ILT3)(+)CD25(+) Treg cells decreased substantially from baseline after 3years of AIT. ILT3(+) Treg cells displayed compromised suppressive function and low FOXP3 expression. In addition, Der p 1-specific IL-10 and IL-22 responses have increased after 30weeks, but only IL-10(+) Der p 1-specific Treg cells remained present at high frequency after 3years of AIT. Increased number of FOXP3(+)Helios(+) and IL-10(+) and decreased ILT3(+) Treg cell responses correlated with improved allergic symptoms. ConclusionThe results indicate that AIT involves upregulation of the activated allergen-specific Treg cells and downregulation of dysfunctional allergen-specific Treg cell subset. Correction of dysregulated Treg cells responses during AIT is associated with improved clinical response.