Myeloid dendritic cells.

There is considerable but as yet incomplete evidence for two developmental lineages of dendritic cells: a myeloid lineage shared with phagocytes and a lymphoid lineage shared with T cells. The two corresponding functional states, which may not require the existence of two formal lineages, are that myeloid dendritic cells capture antigens in the periphery and then migrate to the lymphoid organs to initiate immunity, whereas lymphoid dendritic cells are found in the thymic medulla and lymph node T cell areas and are responsible for tolerance. The latter may occur through immune regulation and/or deletion. Myeloid dendritic cells undergo many activities that contribute to the initiation of immunity. These are summarized here and include mobilization from progenitors and precursors in the blood and marrow, maturation from immature cells in the skin and interstitial spaces, formation of MHC-peptide complexes in MHC class II compartments or MIICs, migration to the T cell areas, and finally, mortality. The death of migratory dendritic cells seems to be accompanied by their phagocytosis and processing by other dendritic cells in the T area. We speculate that this transfer of antigens, including self-peptides captured by the uptake of apoptotic cells in peripheral tissues, is an important prelude to the regulatory function of resident or lymphoid dendritic cells in the T cell area. These features of dendritic cell biology provide targets to manipulate the immune response in vivo.