Pereira-Santos, M. C.Baptista, A. P.Melo, A.Alves, R. R.Soares, R. S.Pedro, E.Pereira-Barbosa, M.Victorino, R. M. M.Sousa, A. E.2014-07-142014-07-142007Clinical and Experimental Allergy, 38, 291–2970954-7894http://hdl.handle.net/10451/11465Journal compilation © 2007 Blackwell Publishing Ltd, Clinical and Experimental Allergy © 2007 The AuthorsBACKGROUND: Venom immunotherapy (VIT) induces long-lasting immune tolerance to hymenoptera venom antigens, but the underlying mechanisms are not yet clarified. Regulatory T cells are thought to play an important role in allergic diseases and tolerance induction during specific immunotherapy. AIM: Characterize longitudinally the impact of VIT on the pool of circulating regulatory T cells. METHODS: Fourteen hymenoptera venom-allergic patients with severe reactions (grades III-IV) were studied before, 6 and 12 months after starting ultra-rush VIT. Freshly isolated peripheral blood mononuclear cells were surface stained with a panel of markers of T cell differentiation and intracellularly for CTLA-4 and Foxp3 and analysed by flow cytometry. foxp3 mRNA was quantified by real-time PCR. VIT responses were assessed by measuring specific IgG4 and IgE levels. Eleven individuals with no history of insect venom allergy were studied as controls. RESULTS: VIT induces a significant progressive increase in both the proportion and the absolute numbers of regulatory T cells defined as CD25bright and/or Foxp3+ CD4+ T cells. These changes are not related to alterations in the expression of activation markers or imbalances in the naïve/memory T cell compartments. foxp3 mRNA levels also increased significantly during VIT. Of note, the increase in circulating regulatory T cell counts significantly correlates with the venom-specific IgG4/IgE ratio shift. CONCLUSION: VIT is associated with a progressive expansion of circulating regulatory T cells, supporting a role for these cells in tolerance induction.engCD25brightFoxp3Regulatory T cellsSpecific immunotherapyVenom allergyjournal articlehttp://dx.doi.org/10.1111/j.1365-2222.2007.02887.x