The hematopoietic development of dendritic cells: a distinct pathway for myeloid differentiation

Dendritic cells (DC) are leukocytes that are specialized to capture antigens and initiate T cell-mediated immune responses. Because DC can prime animals in the absence of any other adjuvant, they have been termed 'nature's adjuvant'. DC express high levels of antigen presenting major histocompatibility complex (MHC) products (HLA-DP, DQ, DR; HLA-A, B, C) as well as several accessory molecules (e.g., B7-1, B7-2, LFA-3, ICAM-1, ICAM-3, CD40) that mediate T cell binding and costimulation. This review outlines some of the ways in which DC are distinguished from two other myeloid lineages, macrophages and granulocytes. Recent data regarding DC development from class II MHC-negative precursors in the mouse, as well as unselected and selected CD34+ progenitors in human bone marrow and peripheral and cord blood, are reviewed. Additional pathways via post-colony-forming units, intermediate cell types have also become evident in suspension cultures where the cytokine milieu can alter terminal differentiation. The availability of larger numbers of DC is opening new avenues for immune therapy that use this physiologic adjuvant.