Natural killer cell-mediated inhibition of bone marrow colony formation (CFU-GM) in refractory anaemia (preleukaemia): evidence for patient-specific cell populations.

The role of peripheral blood mononuclear cells (PB-MNC) on the growth of bone marrow (BM) CFU-GM was investigated in refractory anaemia (RA) patients. Whereas normal donor PB-MNC were found to inhibit autologous day 7 CFU-GM, PB-MNC from RA patients exhibited little modulatory effect on autologous or allogeneic day 7 CFU-GM. In contrast, patient PB-MNC inhibited autologous CFU-GM at day 10 at a time where no significant inhibition was seen in the PB-MNC/RA CFU-GM combination. The identity of the inhibitory cells was investigated using anti-T8+ and anti-N901+ subsets purified by immune-rosette depletion with a panel of monoclonal antibodies. The activity of these subsets was tested on immature myeloid cells enriched for MY7+ cells, and it was found that cells highly enriched for NK cells were responsible for the inhibition. Further support for NK cells as the inhibitory cells was obtained in experiments where a positive correlation between the level of PB NK cytotoxicity against K562 cells and the degree of CFU-GM inhibition was demonstrated. Thus, these data suggest the presence of a specialized subset of NK cells with a capacity to inhibit autologous CFU-GM. Since RA is a potentially premalignant disease, in which a significant number of cases transform into AML, these findings also suggest a physiological role for NK cells in suppression of newly arisen clonogenic cells at least in early stages of the disease.