T regulatory cells in allergy and health: a question of allergen specificity and balance.

Anergy, tolerance and active suppression may not be independent events, but rather involve similar mechanisms and cell types in immune regulation. Induction of allergen-specific regulatory/suppressor T cells (T(Reg)) seems essential for the maintenance of a healthy immune response to allergens. Allergen-specific immunotherapy can induce specific T(Reg) cells that abolish allergen-induced proliferation of T helper 1 (Th1) and Th2 cells, as well as their cytokine production. T(Reg) cells utilize multiple suppressive mechanisms, interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) as secreted cytokines and CTLA-4, PD-1, mTGF-beta, mIL-10, TGF-betaR and IL-10R as surface molecules. An important aspect of T(Reg) cells is the regulation of antibody isotypes and suppression of proinflammatory cells. IL-10 and TGF-beta secreted by T(Reg) cells skew production of IgE towards the noninflammatory isotypes, IgG4 and IgA, respectively. Furthermore, T(Reg) cells may directly or indirectly suppress effector cells of allergic inflammation such as basophils and eosinophils. In conclusion, induction of antigen-specific T(Reg) cells may redirect an inappropriate immune response against allergen or autoantigens with the help of a broad range of suppressor mechanisms.