SUPPRESSION OF NATURAL-KILLER-CELL ACTIVITY BY GRANULOCYTES IN PATIENTS WITH APLASTIC-ANEMIA - ROLE OF GRANULOCYTE-COLONY-STIMULATING FACTOR

Patients with aplastic anemia were tested for natural killer (NK) acti vity, and the roles of granulocytes and granulocyte colony-stimulating factor (G-CSF) in the regulation of cytotoxicity were evaluated. Bloo d lymphocytes showed low or no NK activity against K562 targets. The d epression of NK activity was more frequently recorded for patients who were not in remission and those who received G-CSF administration. Gr anulocytes of aplastic anemia patients with impaired NK activity suppr essed the lytic activity of NK cells. By contrast, granulocytes from n ormal controls and aplastic anemia patients with normal NK activity ha d no suppressive activity. There was a good correlation between NK act ivity of lymphocytes and suppressive activity of granulocytes. Blockin g of direct contact of suppresser and effector cells by cell chambers abolished suppression of cytotoxicity. NK suppression by granulocytes was resistant to treatment with catalase or superoxide dismutase. In v itro stimulation with G-CSF of granulocytes that naturally had no supp ressive activity resulted in development of suppressive function, wher eas granulocytes with natural suppressive activity were not further st imulated in vitro by G-CSF to express augmented activity. These result s suggest that the presence of suppressor granulocytes in the blood co uld be one cause of the impaired NK activity in patients with aplastic anemia.