STEM-CELL FACTOR AUGMENTS TUMOR NECROSIS FACTOR-GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR-MEDIATED DENDRITIC CELL HEMATOPOIESIS

We describe the effects of stem tell factor (SCF) on the dendritic cel l (DC) pathway and provide evidence for the existence of a post granul ocyte-macrophage colony-forming unit (GM-CFU) DC progenitor. When empl oyed with cytokines regulating DC development (tumor necrosis factor [ TNF] + GM colony-stimulating factor [GM-CSF]), SCF increased the size of monocyte (mono) and mono-DC colonies arising from ford blood CD34() progenitor cells. The overall plating efficiency of these colonies i ncreased approximately threefold, as compared with growth in TNF + GM- CSF. Most (similar to 70 %) of the CFUs were mono-DC CFU, and SCF did not alter the proportion of mono-DC CFU to mono-CFU obtained with TNF + GM-CSF alone. Proliferation, as measured by thymidine uptake and man ual cell counts, at lease doubled and occurred earlier (by day 4). In long-term cultures established with TNF + GM-CSF + SCF, high levels of proliferation were prolonged for up to three weeks. These were associ ated with extended DC development and the capacity to form 2 degrees m ono-DC colonies. There was no induction of polymorphonuclear (PMN) cel ls in 2 degrees cultures treated with either GM-CSF, GMCSF + SCF or GM -CSF + granulocyte CSF (G-CSF), implying that the DC progenitor being replated was post GM-CFU. DC progeny arising in the presence of SCF ex hibited typical DC features including: the lack of nonspecific esteras e and phagocytic activity, the presence of class II major histocompati bility complex (MHC) antigens, the absence of CD14 antigens, and the a bility to induce a potent mixed leukocyte reaction. Thus, SCF augments DC growth from progenitor cells without altering the developmental co mmitment instituted by TNF + GM-CSF. This enhancement follows the same general mechanisms previously reported for SCF-mediated lineage enhan cement, i.e., increased colony size, number and plating capacity.