DENDRITIC CELLS AND MACROPHAGES CAN MATURE INDEPENDENTLY FROM A HUMANBONE-MARROW-DERIVED, POST-COLONY-FORMING UNIT INTERMEDIATE

CD34(+) precursors in normal human bone marrow (BM) generate large num bers of dendritic cells alongside macrophages and granulocytic precurs ors when cultured for 12 to 14 days in c-kit ligand, granulocyte-macro phage colony-stimulating factor (GM-CSF), and tumor necrosis factor-al pha (TNF-alpha). This study reports an intermediate cell type that dev elops by day 6, and has the potential to differentiate into either mac rophages or dendritic cells. When the d6 progeny are depleted of matur e macrophages and residual CD34(+) precursors, a discrete CD14(+) HLA- DR(+) population persists in addition to immunostimulatory CD14(-) HLA -DR(+++) dendritic cells. Half of the CD14(+) HLA-DR(+) population is in cell cycle (Ki-67(+)), but colony-forming units (CFUs) are no longe r detectable. The cells are c-fms(+), but lack myeloperoxidase and non specific esterase. They also possess substantial phagocytic and allost imulatory activity. These post-CFU, CD14(+) HLA-DR(+) intermediates de velop into typical macrophages when recultured in the absence of exoge nous cytokines. M-CSF supports up to similar to 2.5-fold expansion of macrophage progeny. In contrast, the combination of GMCSF and TNF-LU s upports quantitative differentiation into dendritic cells, lacking c-f ms, CD14, and other macrophage properties, and expressing HLA-DR, CD1a , CD83, CD80, CD86, and potent allostimulatory activity. Therefore, no rmal CD34(+) BM precursors can generate a post-CFU bipotential interme diate in the presence of c-kit ligand, GM-CSF, and TNF-alpha. This int ermediate cell type will develop along the dendritic cell pathway when macrophages are removed and GM-CSF and TNF-alpha are provided. Altern atively, it can differentiate along a macrophage pathway when recultur ed with or without M-CSF. (C) 1996 by The American Society of Hematolo gy.