Stem cell factor augments tumor necrosis factor‐granulocyte‐macrophage colony‐stimulating factor‐mediated dendritic cell hematopoiesis

Abstract

We describe the effects of stem cell factor (SCF) on the dendritic cell (DC) pathway and provide evidence for the existence of a post granulocyte-macrophage colony-forming unit (GM-CFU) DC progenitor. When employed 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 cord blood CD34⁺ progenitor cells. The overall plating efficiency of these colonies increased approximately threefold, as compared with growth in TNF + GM-CSF. Most (-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 manual cell counts, at least 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 associated with extended DC development and the capacity to form 2* mono-DC colonies. There was no induction of polymorphonuclear (PMN) cells in 2* cultures treated with either GM-CSF, GM-CSF + 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 exhibited typical DC features including: the lack of nonspecific esterase and phagocytic activity, the presence of class II major histocompatibility complex (MHC) antigens, the absence of CD14 antigens, and the ability to induce a potent mixed leukocyte reaction. Thus, SCF augments DC growth from progenitor cells without altering the developmental commitment instituted by TNF + GM-CSF. This enhancement follows the same general mechanisms previously reported for SCF-mediated lineage enhancement, i.e., increased colony size, number and plating capacity.