Are regulatory T cells the target of venom immunotherapy?

Allergen-specific immunotherapy is the only treatment that leads to lifelong tolerance to previously disease-causing allergens by restoring normal immunity against allergens. T-regulatory (T-Reg) cells are involved in preventing sensitization to allergens and represent a major target for venom- or other allergen-specific immunotherapy. Recent findings Induction of peripheral tolerance in T cells, which is characterized mainly by suppressed proliferative and cytokine responses against the T-cell epitopes of major allergens, is an essential step in specific immunotherapy. It is initiated by the autocrine action of interleukin-10 and/or transforming growth factor-beta, which are produced by antigen-specific T-Reg cells. Tolerized T cells can be reactivated to produce distinct T-helper-1 or T-helper-2 cytokine partterns, thus directing allergen-specific immunotherapy toward successful or unsuccessful outcomes. T-Reg cells directly or indirectly influence effector cells of allergic inflammation, such as mast cells, basophils and eosinophils. In addition, there is accumulating evidence that they may suppress IgE production and induce IgG(4) and IgA production against allergens. In addition, histamine released from mast cells and basophils may effectively contribute to immunoregulation during specific immunotherapy, and affect T-Reg cells and the production of their cytokines via histamine receptor 2. Summary By applying recent knowledge in T-Reg cell-dependent mechanisms of peripheral tolerance, more rational and safer approaches to the prevention and cure of venom hypersensitivity may be developed in the future.