SPONTANEOUS CYTOTOXICITY OF HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS TOWARD RED BLOOD-CELL TARGETS .2. TIME-DEPENDENT LOSS OF SUPPRESSOR CELL ACTIVITY

Abstract

Human peripheral blood mononuclear cells were previously shown to become strikingly cytotoxic toward a wide variety of red blood cell targets after 7 days of in vitro culture. The cell responsible for cytotoxicity does not rosette with SRBC [sheep red blood cells] and demonstrates surface adherence and phagocytic properties. This paper shows that development of spontaneous cytotoxicity is due to a time-dependent loss of suppressor cell function. Fresh autologous lymphocytes, when added to cultured cells, abrogate the subsequent expression of spontaneous cytotoxicity toward RBC targets. The suppressor cell is radioresistant; requires 24 h to suppress optimally; is inactivated by heating at 56.degree. C for 15 min, and is enriched in the non-T [thymus-derived] cell interface after SRBC rosette depletion over a discontinuous Ficoll-Hypaque gradient. The addition of a cell-free sonicate of fresh lymphocytes is capable of inhibiting spontaneous cytotoxicity toward RBC targets. If mononuclear cells are allowed to incubate in tissue culture medium for 7 days they are no longer suppressive after sonication. Fresh mononuclear cells apparently exert a potent negative regulatory influence on monocyte killing. By removing this negative influence, a new model of sponataneous non-specific killing by monocytes is produced.