GM-CSF promotes differentiation of a precursor cell of monocytes and Langerhans-type dendritic cells from CD34+ haemopoietic progenitor cells

Epithelia-associated dendritic cells (DC) including Langerhans cells in the skin (LC) are precursors of lymph node located interdigitating DC (iDC). CD1a⁺ LC are known to be derived from CD34⁺ haemopoietic progenitor cells (HPC); however, cells of an intermediate differentiation state that are CD34^? and CD1a^? have not been identified. Monitoring the differentiation pathway of HPC in the presence of GM-CSF + IL-4, we observed the emergence of a distinct LC precursor population that was CD33⁺ CD13⁺ CD4⁺ CD38⁺ CD44⁺ CD34^? CD14^? CD1a^?. The cells could be separated by FACS due to a unique CD44/CD38 expression pattern or by CD44 expression in conjunction with the SSC profile. It was found that they were similarly generated in the presence of GM-CSF alone and were detectable in culture for at least a week. Irrespective of being generated in the presence of GM-CSF + IL-4 or GM-CSF alone, CD44/SSC-sorted precursor cells matured to MHC class II compartments (MIIC) and Birbeck granules (BG) expressing LC, when subsequently cultured in the presence of GM-CSF + IL-4. When IL-4 was omitted, however, the same cells matured to phagocytically active adherent macrophages (MΦ). These culture conditions were associated with a > 4-fold increase in the concentration of IL-6 when compared to those used for LC differentiation. The identification of a distinct oligopotent precursor cell population that can deliberately be induced to give rise to BG⁺ MIIC⁺ CD1a⁺ CD14^? LC or to adherent CD14⁺ MΦ further substantiates the close relationship of monocytes and DC and may help to identify its in vivo equivalent.