Journal Article
. 2007 Dec; 38(2):291-7.
doi: 10.1111/j.1365-2222.2007.02887.x.

Expansion of circulating Foxp3+)D25bright CD4+ T cells during specific venom immunotherapy

M C Pereira-Santos 1 A P Baptista  A Melo  R R Alves  R S Soares  E Pedro  M Pereira-Barbosa  R M M Victorino  A E Sousa  
  • PMID: 18070166
  •     27 citations


Background: 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.

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