Patients with IPEX, which are deficient of CD25+Treg, commonly suffer from organ-specific autoimmune diseases and in addition they develop severe dermatitis, high levels of serum IgE and sometimes eosinophilia. This suggests that CD25+Treg play an important part in the development of tolerance to allergens. We investigated whether the functions of CD25+Treg from birch allergic patients were comparable to those derived from healthy controls and whether their function was influenced by an ongoing allergic reaction . We did not detect any differences in the numbers of either CD25highTreg or the total amount of CD4+CD25+ T cells in peripheral blood of birch allergic patients compared to healthy controls neither out of season nor during birch pollen season. Furthermore, both groups potently suppressed T-cell proliferation and IFN-γ production in response to birch allergen irrespectively of whether it was out of or during birch pollen season. The allergic immune response is characterized by the production of Th2 cytokines IL-4, IL-5 and IL-13, which leads to secretion of allergen-specific IgE and recruitment of eosinophils . The ability of CD25+Treg to suppress production of Th2 cytokines would therefore be particularly desired. Interestingly, during season, CD25+Treg from birch allergics, but not from nonallergic controls, were unable to suppress birch pollen-induced IL-13 and IL-5 production, a difference that was not observed in cultures with soluble anti-CD3 Ab stimulation. In contrast, out of season, both allergics and nonallergics suppressed IL-13 and allergics also inhibited IL-5 production from CD25– T cells. Conclusively, this does not suggest a general deficiency of the CD25+Treg in birch allergic patients. However, in season, during an ongoing allergic reaction with already activated effector T cells present, CD25+Treg from birch allergics are less able to downregulate Th2 cytokines. It has been shown that increased levels of IL-4 obstruct the suppressive ability of CD25+Treg to suppress Th2 clones . Since allergic individuals produce IL-4 when exposed to allergen, this might be one explanation for the deficient regulation of Th2 cytokines during birch pollen season. Alternatively, strongly activated birch-specific T cells might be more resistant to suppression . In accordance with our results, others have shown that CD25+Treg derived from peripheral blood of patients allergic to cow milk or grass or birch pollen suppressed allergen-induced proliferation [104, 116]. Variable effects of CD25+Treg have been reported with regard to the suppression of Th2 cytokines in allergy. In support of our study, Bellinghausen et al.  found that CD25+Treg from a subpopulation of their allergic subjects, which produced higher levels of IL-4, were unable to suppress the production of IL-5 from CD25– T cells. Ling et al.  reported that patients suffering from hayfever were less capable of suppressing both proliferation and IL-5 production during the grass pollen season as compared to nonatopic individuals and that this defect remained also outside season although to lesser extent. CD25+Treg from nickel-allergic patients did not suppress nickel-specific T-cell proliferation to the same extent as healthy individuals did . However, since the immunological mechanisms involved in nickel and pollen allergy are very different, it is not surprising that different results are generated from these two patient groups.