Thymus-homing dendritic cells in central tolerance.

Central tolerance is critical in establishing a peripheral T-cell repertoire purged of functional autoreactive T cells. One of the major requirements for effective central tolerance is the presentation of self and other innocuous antigens (Ags), including food, gut flora, or airway allergens, to developing T cells in the thymus. This seemingly challenging task can be mediated in some cases by ectopic expression of tissue-specific Ags by thymic epithelial cells or by entry of systemic blood-borne Ags into the thymus. More recently, thymic homing peripheral dendritic cells (DCs) have been proposed as cellular transporters of peripheral tissue-specific Ags or foreign innocuous Ags. The aim of this viewpoint is to discuss the three principal thymic DC populations and their trafficking properties in the context of central tolerance. We will first discuss the importance of peripheral DC trafficking to the thymus and then compare and contrast the three DC subsets. We will describe how they were characterized, describe their trafficking to and their microenvironmental positioning in the thymus, and discuss the functional consequence of thymic trafficking and localization on thymic selection events.