Signals from dying cells: tolerance induction by the dendritic cell.

Uncontrolled immune responses are central to the pathogenesis of sustained viral infection, tumor growth, autoimmune diseases, and organ rejection. Dendritic cells (DCs) are critical to determining the outcome of immune responses by directing the function of T-cells. When DCs encounter antigen together with maturation signals immunity results; however, when they encounter apoptotic cells immune tolerance can be induced. It is thought that this is a mechanism to help prevent responses to self antigens because apoptotic cells can enter antigen-processing pathways. Our interest is the mechanisms by which DCs induce tolerance to the antigens associated with apoptotic cells. Here, we examine evidence showing a pivotal role for interleukin-10 (IL-10) in regulating the response of DCs to apoptotic cells. We show that although tolerogenic DCs are CD11c+ and CD8alpha+, the important DCs reside in a subpopulation of these cells that also express IL-10R. Current studies are designed to isolate and characterize this extremely small, but potent, subpopulation of tolerance-inducing DCs.