NATURAL-KILLER (NK) CELLS INHIBIT HUMAN UMBILICAL-CORD BLOOD ERYTHROPOIESIS

To examine the role of NK cells on in vitro human umbilical cord (HUG) blood erythropoietic progenitor growth, 25 normal HUC blood samples were depleted of CD56(+) cells by using immunomagnetic beads coated with CD56 monoclonal antibodies (mAb). When stimulated by erythropoietin (Epo) to form colonies in plasma clot medium, the CD56(+)-depleted preparations demonstrated a two-fold increase in the number of early erythropoietic progenitors (BFU-E) over nondepleted preparations. This stimulatory effect of CD56(+) depletion on BFU-E growth was not due to artifactual, stimulations of other accessory cells by the mAb or the dynabeads used in the depletion procedure, since separate addition of these materials to culture did not exert any stimulatory effect on BFU-E growth. Direct co-culture of purified NK and autologous cord blood mononuclear cells (MNC) in plasma clot medium resulted in a dose-dependent decrease in BFU-E population. In addition, when NK and MNC were cocultured separately in double-layer cultures, the expansion of BFU-E was significantly decreased. Because direct cell-to-cell contact is prohibited in double-layer cultures, the observed inhibition of BFU-E proliferation could be mediated at least in part through soluble factors. To test this hypothesis, NR cell supernatant fluid obtained 24 hours after NK cell. incubation was added to plasma clot culture medium. A significant decrease in BFU-E number was again observed. In conclusion, our results indicate that HUC blood BFU-E proliferation is inhibited by NK cells, and that the mechanism of this inhibition is mediated, at least in part, by one or more humoral factors.