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Background CD4+CD25+ regulatory T (Treg) cells and the cytokines IL-10 or TGF-β play key roles in the maintenance of T cell homeostasis and tolerance to infectious and non-infectious antigens such as allergens. Objective To investigate the regulation of immune responses to birch pollen allergen compared with influenza antigen by Treg cells obtained from birch pollen-allergic patients and non-allergic controls. Methods Peripheral blood was collected from 10 birch pollen-allergic patients and 10 non-allergic healthy controls. CD4+CD25+ and CD4+CD25− cells isolated by magnetic-activated cell sorting were co-cultured and stimulated with birch pollen extract or influenza vaccine in the absence or presence of anti-IL-10 or soluble TGF-βRII. Results CD4+CD25+ cells from non-allergic controls were able to suppress influenza antigen and birch pollen stimulated effector cell proliferation, whereas CD4+CD25+ cells from allergic patients suppressed influenza antigen-, but not birch pollen-stimulated proliferation. The production of Th1 cytokines, but not Th2 cytokines, was suppressed by CD4+CD25+ cells from both allergic patients and controls, upon stimulation with birch pollen extract. Neutralization of IL-10 led to significantly increased production of IFN-γ in cultures with CD4+CD25− T effector cells. In addition, six-fold higher concentrations of TNF-α were detected after neutralization of IL-10 in both CD4+CD25− and CD4+CD25+ cell cultures from allergic patients and controls. Conclusion We demonstrate that the allergen-specific suppressive function of CD4+CD25+ cells from allergic patients is impaired compared with non-allergic controls. Moreover, neutralization of IL-10 enhances the production of TNF-α, suggesting counter-acting properties of IL-10 and TNF-α, where IL-10 promotes tolerance and suppression by Treg cells and TNF-α promotes inflammatory responses. [ABSTRACT FROM AUTHOR]