Normal non-adherent mononuclear cells were shown to inhibit colony formation by normal human marrow cells cultured for 7 d in semi-solid agar. Inhibition was the same using cells from the marrow donor or from an unrelated normal subject, and was shown to be dose-dependent over the range of 4 X 10(5) to 6 X 10(3) mononuclear cells per 1 X 10(5) marrow cells plated. Inhibition was not seen in 14 d cultures, and it is postulated that colony-forming cells sensitive to lymphocyte inhibition belonged to the population known to give rise to colonies after 7 d in culture. Cell fractionation studies showed that inhibition was due to non-B non-T lymphocytes, purified B cells or T cells being neither inhibitory nor stimulatory. Inhibition was only shown with intact viable lymphocytes and it was not possible to extract inhibitory activity from the cells, or to produce inhibition by media conditioned by lymphocytes. The effect was apparently due to a direct action on colony-forming cells in the marrow and was not due to inhibition of colony stimulating activity (CSA) production, or to absorption or inactivation of CSA. These results emphasize the need to include appropriate controls when looking for possible cell-mediated inhibitors in disease states, particularly when 7 d cultures are used.

No abstract

Peripheral blood lymphocytes from 20 patients with neutropenia not consistent with aplastic anaemia were tested for their ability to inhibit the proliferation of normal granulopoietic precursor cells (CFU-GM) in agar culture. Two patients, both with features of an autoimmune disorder, had lymphocytes which were more inhibitory than normal lymphocytes to both normal and their own CFU-GM. Two other patients had lymphocytes which were more inhibitory than normal lymphocytes to either their own CFU-GM or normal CFU-GM but not both. Eight patients had lymphocytes which were significantly less inhibitory than normal lymphocytes to either normal or their own CFU-GM, but only one showed this feature against both normal and their own CFU-GM. One patient had a highly potent plasma inhibitor of CFU-GM--this patient had received multiple transfusions and had a leucocyte antibody of a broad specificity. No clinical or haematological features were common to any of these groups of patients which reflects the heterogeneity of patients studied and stresses the importance of controls.

No abstract

Culture of bone marrow and/or blood cells in a semisolid agar system from 43 adults with acute nonlymphoblastic leukemia at first presentation showed two distinct growth patterns at 14 days. In 53% of patients cells failed to grow (type O), while in the remainder an abnormal growth pattern (type B) with small numbers of diffuse colonies and excessive numbers of cell clusters was seen. The response following chemotherapy was significantly better in the patients whose cells failed to grow. Serial culture studies, performed in 9 patients throughout remissions of 100–1112 days, which had been maintained by intermittent chemotherapy, showed wide fluctuations in proliferative activity. These ranged from no growth to marked proliferation with predominance of clusters and small numbers of diffuse colonies, indistinguishable from the type B pattern seen in 47% of patients at first presentation. The possibility is discussed that the periods of failure to grow, and/or those in which a type B pattern emerged, represented sporadic reactivation of leukemic cells.