Dendritic cells: immune regulators in health and disease

Dendritic cells (DCs) are bone marrow-derived cells of both lymphoid and myeloid stem cell origin that populate all lymphoid organs including the thymus, spleen, and lymph nodes, as well as nearly all nonlymphoid tissues and organs. Although DCs are a moderately diverse set of cells, they all have potent antigen-presenting capacity for stimulating naive, memory, and effector T cells. DCs are members of the innate immune system in that they can respond to dangers in the host environment by immediately generating protective cytokines. Most important, immature DCs respond to danger signals in the microenvironment by maturing, i.e., differentiating, and acquiring the capacity to direct the development of primary immune responses appropriate to the type of danger perceived. The powerful adjuvant activity that DCs possess in stimulating specific CD4 and CD8 T cell responses has made them targets in vaccine development strategies for the prevention and treatment of infections, allograft reactions, allergic and autoimmune diseases, and cancer. This review addresses the origins and migration of DCs to their sites of activity, their basic biology as antigen-presenting cells, their roles in important human diseases and, finally, selected strategies being pursued to harness their potent antigen-stimulating activity.