Activation-induced cell death, anergy and/or immune response modulation by T regulatory cells (TReg) are essential mechanisms of peripheral T-cell tolerance. There is growing evidence that anergy, tolerance and active suppression are not entirely distinct, but rather, represent linked mechanisms possibly involving the same cells and multiple suppressor mechanisms. Skewing of allergen-specific effector T cells to TReg cells appears as a crucial event in the control of healthy immune response to allergens and successful allergen-specific immunotherapy. The TReg cell response is characterized by abolished allergen-induced specific T-cell proliferation and suppressed T helper 1 (Th1)- and Th2-type cytokine secretion. The increased levels of interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) that are produced by TReg cells, potently suppress IgE production, while simultaneously increasing production of noninflammatory isotypes IgG4 and IgA, respectively. In addition, TReg cells directly or indirectly suppress effector cells of allergic inflammation such as mast cells, basophils, and eosinophils. In conclusion, peripheral tolerance to allergens is controlled by multiple active suppression mechanisms. It is associated with regulation of antibody isotypes and effector cells to the direction of a healthy immune response and opens a window for novel therapies of allergic diseases. Copyright © 2006 S. Karger AG.
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