SPECIFIC INHIBITORY ACTIVITY AGAINST GRANULOCYTE-PROGENITOR CELLS PRODUCED BY NON-T-LYMPHOCYTES FROM PATIENTS WITH NEUTROPENIA

Abstract

Bone marrow and peripheral blood cells of patients with non-leukemic neutropenia contain and elaborate a granulocyte-progenitor cell inhibitory activity. The inhibitory activity is common to the neutropenias of the various etiologies studied, which included congenital, idiopathic, autoimmune, cyclical, common variable immunodeficiency with hypogammaglobulinemia and drug induced states. It derives from non-adherent, low density, slowly sedimenting and non-E[erythrocyte]-rosetting cells and appears to require RNA and protein synthesis, but not cell division, for its production. The material is not species specific, inhibits autologous and allogeneic normal CFUgm (granulocyte-macrophage colony-forming cells) and leukemic CFUgm, is not cell-cycle specific in action and is most effective against granulocyte colony-forming cells (CFUg), less effective against mixed CFUgm and least or non-effective against macrophage colony-forming cells (CFUm). This inhibitory activity has no influence on cells which generate CFUc [granulocytic progenitor cells] in suspension culture or on the erythroid colony-forming (CFUe) and erythropoietic burst-forming (BFUe) units. It is different from other known inhibitory activities such as lactoferrin, leukemia inhibitory activity, E type prostaglandins, interferon and Ig. This inhibitory activity, while at present an in vitro phenomenon, may be produced as a secondary response within an immuno-compromised host.