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 w ere depleted of CD56(+) cells by using immunomagnetic beads coated wit h CD56 monoclonal antibodies (mAb). When stimulated by erythropoietin (Epo) to form colonies in plasma clot medium, the CD56(+)-depleted pre parations demonstrated a two-fold increase in the number of early eryt hropoietic progenitors (BFU-E) over nondepleted preparations. This sti mulatory effect of CD56(+) depletion on BFU-E growth was not due to ar tifactual, stimulations of other accessory cells by the mAb or the dyn abeads used in the depletion procedure, since separate addition of the se materials to culture did not exert any stimulatory effect on BFU-E growth. Direct co-culture of purified NK and autologous cord blood mon onuclear cells (MNC) in plasma clot medium resulted in a dose-dependen t decrease in BFU-E population. In addition, when NK and MNC were cocu ltured separately in double-layer cultures, the expansion of BFU-E was significantly decreased. Because direct cell-to-cell contact is prohi bited in double-layer cultures, the observed inhibition of BFU-E proli feration could be mediated at least in part through soluble factors. T o test this hypothesis, NR cell supernatant fluid obtained 24 hours af ter NK cell. incubation was added to plasma clot culture medium. A sig nificant decrease in BFU-E number was again observed. In conclusion, o ur results indicate that HUC blood BFU-E proliferation is inhibited by NK cells, and that the mechanism of this inhibition is mediated, at l east in part, by one or more humoral factors.