title: GM-CSF promotes differentiation of a precursor cell of monocytes and Langerhans-type dendritic cells from CD34+ haemopoietic progenitor cells.
abstract: 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 (Mphi). 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+ Mk further substantiates the close relationship of monocytes and DC and may help to identify its in vivo equivalent.
authors.affiliation: Department of Biology, University of Freiburg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Herbst
authors.forename: G
authors.initials: G
authors.lastname: Köhler
authors.forename: A
authors.initials: A
authors.lastname: Mackensen
authors.forename: H
authors.initials: H
authors.lastname: Veelken
authors.forename: A
authors.initials: A
authors.lastname: Lindemann
mesh_terms: D018952:Antigens, CD34 / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007801:Langerhans Cells / Q000166:cytology*; D008854:Microscopy, Electron; D009000:Monocytes / Q000166:cytology*; D010641:Phenotype
chemical_list: D018952:Antigens, CD34; D016178:Granulocyte-Macrophage Colony-Stimulating Factor