Direct synergistic effects of interleukin-7 on in vitro myelopoiesis of human CD34+ bone marrow progenitors

Abstract

Interleukin-7 (IL-7) is an important growth factor in B and T lymphopoiesis in mouse and human, whereas IL-7 has been regarded to lack proliferative effects on cells within the myeloid lineage. However, we have recently reported that IL-7 potently can enhance colony stimulating factor (CSF)-induced myelopoiesis from primitive murine hematopoietic progenitors, showing a novel role of IL-7 in early murine myelopoiesis. Using CD34+ human hematopoietic progenitor cells, we show here a similar role of IL-7 in human myelopoiesis, although interesting differences between the two species were found as well. Although purified recombinant human (rh)IL-7 alone did not induce any proliferation of CD34+ cells, IL-7 in a concentration-dependent manner enhanced the colony formation induced by all four CSFs up to threefold. Furthermore, stem cell factor (SCF)-induced granulocyte-macrophage (GM) colony formation was increased fourfold in the presence of IL-7. Single- cell cloning assays showed that these synergistic effects of IL-7 were directly mediated on the targeted progenitors, and that IL-7 increased the number, as well as the size of the colonies formed. Morphological examination showed that IL-7 affected the progeny developed from CD34+ cells stimulated by G-CSF or IL-3, increasing the number of CFU-M (colony forming unit-macrophage) and CFU-granulocyte-macrophage, whereas the number of CFU-granulocyte were unaltered.