Development and function of dendritic cells in health and disease.

The life history of dendritic cells (DC) is now established from their origins from bone marrow stem cells, their distribution through blood to the tissues, and their movement via afferent lymph to lymph nodes for the initiation of immune responses. Bone-marrow stem cells, and occasional stem cells in peripheral blood (about 1 per 10(5) mononuclear cells), can give rise both to DC and macrophages (MO). In addition to stem cells in blood, after short-term culture of mononuclear cells, three major morphologic types of DC can be separated (types I-III), which probably represent the maturational pathway of this cell type; type II cells resemble tissue DC such as Langerhans cells and type III have a veiled morphology similar to that seen in cells of afferent lymph and in the interdigitating cells of the paracortex of lymph nodes. Functionally, DC cultured from peripheral blood are able to acquire large antigens and process them like Langerhans cells of the skin. They can also present antigens to stimulate primary T-cell responses, a property associated with lymph node DC. In tissues, DC appear to act as outposts of the immune system, acquire antigens, and, particularly in primary responses, carry the antigens to lymph nodes where they initiate T-cell responses. In secondary responses, activation of memory T cells in the periphery and the acquisition of antigen/antibody complexes by follicular dendritic cells of the lymph node follicles, which stimulate B cell memory, may be more important pathways for immune activation. DC may play a role in the development of many immunologic diseases including cancer, autoimmunity, and acquired immunodeficiency syndrome (AIDS).