Adaptive T-cell responses regulating oral tolerance to protein antigen

The term oral (or mucosal) tolerance has been classically defined as the suppression of T- and B-cell responses to an antigen by prior administration of the antigen by the oral route. In recent years, it has become clear that both innate and acquired regulatory immune responses are essential for the development of oral tolerance. As such, mucosal microenvironmental factors such as transforming growth factor- β, prostaglandins but also dietary vitamin A create conditioning of an adaptive regulatory T-cell response that suppresses subsequent antigen-specific responses. Particular resident subsets of antigen presenting dendritic cells are pivotal to convey conditioning signals next to the presentation of antigen. This review discusses the primary mechanisms of adaptive regulatory T-cell induction to ingested soluble protein antigen. However, we also discuss the limitations of our knowledge with respect to understanding the very common food hypersensitivity Celiac disease caused by an aberrant adaptive immune response to the food protein gluten.