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.
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-allergicpatients 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.
Authors: Lisa M Kosloski; Elizabeth A Kosmacek; Katherine E Olson; R Lee Mosley; Howard E Gendelman Journal: J Neuroimmunol Date: 2013-10-29 Impact factor: 3.478
Authors: Mark S Wilson; John T Pesce; Thirumalai R Ramalingam; Robert W Thompson; Allen Cheever; Thomas A Wynn Journal: J Immunol Date: 2008-11-15 Impact factor: 5.422