Induction of CD4+CD25+Foxp3+IL-10+ T Cells in HDM-Allergic Asthmatic Children with or without SIT

Abstract

Background: Regulatory T cells and immunosuppressive cytokines, such as IL-10 and TGF-β₁, may have a role in clinically effective allergen-specific immunotherapy. IL-10-secreting regulatory T cells have emerged as potential mediators of immune tolerance in numerous murine models of immunopathology. The aim of this study was to evaluate the frequency and function of regulatory T cells in the response to house dust mite (HDM) immunotherapy. Methods: PBMCs were isolated from 27 HDM-allergic asthmatic children who underwent immunotherapy for 1.5–2 years (SIT group) and from 27 matched treated asthmatic children allergic to HDM (asthma group). After 48 h of in vitro stimulation with HDM extracts, regulatory T cells were measured by flow cytometry. Production of IL-4, IFN-γ and TGF-β₁in supernatants from allergen-stimulated cultures and the PBMC proliferations were measured by ELISA. Sera were tested for allergen-specific IgE using the ImmunoCAP 100 assay. Results: Patients undergoing immunotherapy produced significantly more IL-10 and showed a significant reduction in proliferation induced by HDM extract compared with the asthma group. In cultures stimulated with HDM extract, the amounts of IL-4 and TGF-β were lower and the amounts of IFN-γ were higher in the SIT group compared with the asthma group. Conclusion: There is a functional, but quantitative, insufficiency of Treg cells in allergic asthmatic children, which was reversed in SIT-treated children. SIT can up-regulate the function of CD4⁺CD25⁺Foxp3⁺ Treg cells.