License to heal: Bidirectional interaction of antigen-specific regulatory T cells and tolerogenic APC

Naturally occurring CD4(+)CD25(+) regulatory T (T,) cells, a component of the innate immune response, which play a key role in the maintenance of self-tolerance, have become the focus of numerous studies over the last decade. These cells inhibit the immune response in an Ag-nonspeciflic manner, interacting with other T cells. Much less is known about adaptive T-R cells, which develop in response to chronic antigenic stimulation, and act directly on professional and nonprofessional APG rendering them tolerogenic and able to elicit the differentiation of CD8(+) and CD4(+) T cells with suppressive activity. In this review, we will discuss data pertaining to the bidirectional interaction between Ag-specific T-R with APC and their clinical relevance.