Background: Allergen-specific immunotherapy (SIT) is a highly effective treatment for allergic diseases, but the underlying mechanisms are unclear. In this study, we investigated the effects of cluster SIT with Dermatophagoides pteronyssinus (Der p) on IL-10-secreting type I T regulatory (Tr1) cells in Der p-sensitized patients with allergic rhinitis. Methods: This was a prospective randomized study involving 68 participants (aged 18-60 years) of whom 38 were patients with allergic rhinitis and received Der p-SIT for 1 year and 30 were nonallergic controls. IL-10+IL-4-CD4+T cells were measured by flow cytometry for the patient group at baseline and at the end of 1 year of SIT, and for nonallergic controls. Similarly, IL-10 in supernatants from allergen-stimulated peripheral blood mononuclear cell (PBMC) cultures were measured by ELISA, and the suppressive effect of Tr1 cells on cell proliferation and cytokine release (IFN-gamma and IL-4) in PBMCs was estimated in cultures from both groups. Allergen-specific serum IgE and IgG4 were also assessed by RAST and ELISA for the SIT group. Results: The levels of IL-10-secreting Tr1 cells, IgG4 and allergen-induced IL-10 synthesis from PBMC cultures were significantly increased and the function of In cells was enhanced after 1 year of SIT compared to baseline levels. In contrast, the level of IgE was not significantly changed. Conclusion: These data suggest that the cluster Der p-SIT may enhance the frequency and function of IL-10-secreting Tr1 cells. Copyright (C) 2012 S. Karger AG, Basel