Immune regulation by CD4+CD25+ T cells and interleukin‐10 in birch pollen‐allergic patients and non‐allergic controls

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Abstract
Summary: 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.