Antigen-specific regulatory T-cell responses against aeroantigens and their role in allergy

The mucosal immune system of the respiratory tract is specialized to continuously monitor the external environment and to protect against invading pathogens, while maintaining tolerance to innocuous inhaled particles. Allergies result from a loss of tolerance against harmless antigens characterized by formation of allergen-specific Th2 cells and IgE. Tolerance is often described as a balance between harmful Th2 cells and various types of protective "regulatory" T cells. However, the identity of the protective T cells in healthy vs. allergic individuals or following successful allergen-specific therapy is controversially discussed. Recent technological progress enabling the identification of antigen-specific effector and regulatory T cells has significantly contributed to our understanding of tolerance. Here we discuss the experimental evidence for the various tolerance mechanisms described. We try to integrate the partially contradictory data into a new model proposing different mechanism of tolerance depending on the quality and quantity of the antigens as well as the way of antigen exposure. Understanding the basis of tolerance is essential for the rational design of novel and more efficient immunotherapies.