The role of allergen-specific regulatory T cells in the control of allergic disease.

Allergies result from an antigen-specific loss of tolerance against innocuous foreign substances. Allergen immunotherapy (AIT) aims to reverse the pathogenic response and to re-establish physiological tolerance. However, the tolerogenic mechanisms that prevent allergy in healthy and act during AIT are still obscure. Foxp3 expressing 'regulatory' CD4 T cells (Tregs) are essential mediators of tolerance against allergens. It remains controversial which antigen specificity of Tregs is required to prevent allergy and the role of allergen-specific Tregs during AIT. Recent work provided precise insight into physiological T cell responses against environmental and food compounds. This identified Treg responses mainly against peptides and proteins not involved in immune pathology, revealing an unexpected role of Treg antigen specificity for tolerance. This review will focus on antigen-specific Treg responses against food and airborne allergens, and the impact of the technological approach utilized for antigen-specific Treg characterization is discussed, with critical points to be addressed in future research.