CYTOTOXIC LYMPHOCYTE MATURATION FACTOR (INTERLEUKIN-12) IS A SYNERGISTIC GROWTH-FACTOR FOR HEMATOPOIETIC STEM-CELLS

The recently cloned cytotoxic lymphocyte maturation factor (interleuki n 12 [IL-12]) has been described as a growth factor for mature lymphoc ytes. The present study investigated whether purified recombinant muri ne IL-12 (rMuIL-12) also could affect the proliferation of primitive b one marrow progenitor cells. Using a population of Lin-Sca-1+ murine b one marrow stem cells, we now demonstrate that IL-12 is a potent syner gistic factor for primitive hematopoietic tem cells. The synergy of IL -12 was observed in single-cell cloning assays, demonstrating that its effects are directly mediated. Specifically, IL-12 enhanced stem cell factor-induced myelopoiesis of Lin-Sca-1+ cells sevenfold, and synerg ized with colony-stimulating factors (CSFs) to induce proliferation of Lin-Sca-1+ stem cells. IL-12 increased the number of responding proge nitor cells as well as the size of the colonies formed. IL-12 also inc reased colony formation of high proliferative potential colony-forming cells with multiple CSF combinations. The effects of IL-12 were conce ntration dependent with a 50% effective dose of 2-20 and 20-200 ng/ml, resulting in maximum stimulation. Furthermore, a neutralizing anti-IL -12 antibody blocked the synergistic effects of rMuIL-12. In addition, IL-12 was found to have synergistic effects on more committed bone ma rrow progenitors as well. Our results therefore suggest that in additi on to being a potent lymphopoietic stimulator, IL-12 is a regulator of the growth of hematopoietic stem cells and their myeloid progeny.