Der p 1-specific Treg and Breg cells in allergen immunotherapy and mechanism of immune tolerance

Abstract

Allergen-specific immunotherapy (AIT) involves the repeated administration of allergen products in order to induce clinical and immunologic tolerance to the offending allergen. The generation and maintenance of functional allergen-specific regulatory T (Treg) cells and regulatory B (Breg) cells are known in bee venom immunotherapy. However, in aeroallergen, house dust mite has not to be studied. The aim of the study is to identify the possible roles of Der p 1-specific active Treg (FOXP3+Helios+CD25+CD127-CD4+), ineffective Treg (ILT3-CD25+CD4+) and Breg (IL-10+IL-1RA+CD73-CD25+CD71+) cells changes during AIT and its correlation to treatment outcomes. We studied 25 allergic patients (20 responders and 5 non-responders) undergoing subcutaneous house dust mite immunotherapy. House dust mite-specific Treg cells responses were investigated by characterization of Der p 1-MHC-class II tetramer-positive cells. House dust mite-specific B cells were detected using fluorochrome-labeled Der p 1 method. Der p 1-specific Treg and Breg cells were analysed by flow cytometry and correlated to clinical response to AIT. We demonstrated that AIT induced activated Der p 1-specific Treg cells and decreased substantially ineffective Der p 1-specific Treg cells. For B cell responses, we found a significant increase of IL-10-and IL-1RA-producing Breg cells after AIT in responding patients. In conclusion, AIT-induced clinical improvement is significantly correlated with the increased of Der p 1-specific Treg and Breg cells.