SYNERGISTIC CYTOTOXICITY .1. CHARACTERIZATION OF A HEAT LABILE PLASMA FRACTION THAT INDUCES NONSPECIFIC CYTOTOXICITY BY HUMAN MONONUCLEAR-CELLS

Abstract

The mechanism by which non-immune mononuclear cells recognize invading foreign material and are activated for cytotoxic attack was studied in a model system employing human mononuclear cells, fresh plasma and 51Cr-labeled xenogeneic target erythrocytes. In these experiments, fresh antibody[Ab]-depleted plasma or mononuclear leukocytes alone were poorly cytotoxic to xenogenic erythrocytes. These target cells were rapidly lysed when fresh Ab-depleted plasma and mononuclear cells were present in the assay. The plasma factor could not be removed by extensive absorption with the target cells, was present in plasma from hypogammaglobulinemic patients, was heat-labile and was sensitive to incubation with zymosan and cobra venom factor. The antigen specificity of this reaction was directed by the serum factor, since target cells autologous to the effector cells could be killed in the presence of Ab-depleted xenogeneic plasma, but not autologous plasma. An important mechanism for the recognition of foreignness by non-immune mononuclear cells may be via interaction with a plasma component, possibly a factor related to serum complement.