Sublingual immunotherapy induces IL-10–producing T regulatory cells, allergen-specific T-cell tolerance, and immune deviation

BackgroundThe immunologic mechanisms underlying sublingual immunotherapy (SLIT) are still unclear, particularly the role of regulatory T cells.ObjectiveWe sought to characterize allergen-specific T-cell responses during successful birch pollen SLIT.MethodsProliferation of PBMCs and PBMCs depleted of CD25+ cells obtained from 9 patients before, after 4 weeks, and after 52 weeks of SLIT was assessed in response to the major birch pollen allergen Bet v 1, the homologous apple allergen Mal d 1, or tetanus toxoid. Allergen-induced cytokine responses and FoxP3 expression of T cells were analyzed by using real-time PCR. The role of IL-10 for regulatory activity of T cells was investigated.ResultsAfter 4 weeks, higher frequencies of circulating CD4+CD25+ T cells were detected together with increased FoxP3 and IL-10 and reduced IL-4 and IFN-γ mRNA expression levels compared with those before SLIT. Proliferation to all 3 antigens was markedly reduced but increased significantly after depletion of CD25+ cells or addition of anti–IL-10 antibodies. After 52 weeks, proliferation in response to Mal d 1 or tetanus toxoid returned to pre-SLIT levels, whereas Bet v 1–induced proliferation remained significantly suppressed and was enhanced by neither depletion of CD25+ cells nor addition of anti–IL-10 antibodies. In parallel, increased IFN-γ and reduced IL-4, IL-10, and FoxP3 mRNA expression was detected. Neither TGF-β levels nor cell-cell contact–mediated suppression of CD4+CD25+ cells changed during the course of SLIT.ConclusionSLIT induces regulatory T-cell suppression through IL-10 during the early phase and specific nonreactivity and immune deviation of allergen-specific T cells during the later phase of therapy.Clinical implicationsSLIT induces immune mechanisms comparable with subcutaneous specific immunotherapy.