Differential responses of fetal, neonatal, and adult myelopoietic progenitors to interferon and tumor necrosis factor

Abstract

Human fetal liver (FL) and neonatal cord blood (CB) granulocyte-monocyte colony-forming progenitor cells (GM-CFC) are unique in their physiological environment and in certain proliferative and differentiative capacities. Tumor necrosis factor (TNF) and interferon (IFN) may inhibit or stimulate the growth of human bone marrow GM-CFC in vitro. The effects of recombinant human (rh) TNF-alpha, rhIFN-alpha, and rhIFN-tau on recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF)-stimulated clonogenic cultures of day 7 GM-CFC from FL and umbilical CB were compared with rhGM-CSF-stimulated GM-CFC from normal human bone marrow (BM). We demonstrate that, in comparison to BM progenitor cells, GM-CFC from both FL and CB were highly resistant to growth inhibition by all three cytokines. Furthermore, clonogenic growth of progenitors from FL and CB was markedly potentiated by IFN-tau in GM-CSF-stimulated cultures and was stimulated by IFN-tau in the absence of GM-CSF. Depletion of potential accessory cells resulted in a marked stimulatory response of CB cells to TNF-alpha, in the presence of GM-CSF, while it did not alter the responses to IFN. The stimulatory effects of IFN-tau and TNF-alpha may be indirectly mediated, at least in part, through induction of increased GM-CSF production and increased GM-CSF receptor expression by fetal cells. Divergent responses of myelopoietic cells, derived from various hematopoietic compartments, to regulatory actions of cytokines may provide a basis for further understanding the role of the environment in maturation and differentiation of granulocytes and monocytes.