Induction of CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup>IL-10<sup>+</sup> 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-beta(1), 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-gamma and TGF-beta(1 )in 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-beta were lower and the amounts of IFN-gamma 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.