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The effector cell in human antibody-dependent cytotoxicity was studied by means of various cell fractionation methods. A strong decrease of cytotoxicity was observed in cell suspensions depleted of lymphocytes forming rosettes with human erythrocytes sensitized with human IgG (EA-RFC) either by gradient centrifugation of rosettes or by fractionation on immune complex Degalan columns. The EA-RFC-depleted, ineffective cell suspensions contained considerable proportions of Ig-positive lymphocytes. In contrast, a marked increase in both cytotoxicity and the proportion of EA-RFC was observed after depletion of T-lymphocytes forming rosettes with sheep erythrocytes by gradient centrifugation. The net effect of the presence of monocytes was to diminish cytotoxicity as measured by chromium release, probably because phagocytized target cells were protected from extracellular lysis. It is concluded that antibody-dependent cytotoxicity in man is mediated by a lymphocyte-like cell that has receptors for the Fc part of IgG but lacks conventional B- and T-lymphocyte markers.

The cells participating in phytohemagglutinin (PHA) and concanavalin A (Con A) induced cytotoxicity mediated by human lymphoid cells were studied by means of various cell fractionation methods. A considerable decrease of cytotoxicity induced by these mitogens was observed in cell suspensions depleted of T lymphocytes forming rosettes with sheep erythrocytes, by gradient centrifugation. Also, depletion of Fc-receptor-bearing lymphoid cells, either by gradient centrifugation or by fractionation on immune complex Degalan columns, led to a marked reduction of the cytotoxic response to PHA and Con A. Our data indicate that optimal cytotoxicity induced by activation with PHA or Con A requires the presence of least two populaitons of lymphoid cells, of thymus as well as non-thymus origin.

Experiments were carried out in order to throw light on the role of cyclic AMP and cyclic GMP in the modulation of the expression of antibody-dependent cytotoxicity mediated by human peripheral blood lymphocytes in vitro. Chicken erythrocytes were used as target cells. Support for an inhibitory role of cyclic AMP was derived from the marked suppression of cytotoxicity by dibutyryl cyclic AMP. Cyclic AMP itself had little effect. Isoproterenol, prostaglandin E1 and prostaglandin E2 increased cyclic AMP concentrations and strongly inhibited the cytotoxic effect of the lymphocytes. Histamine showed very slight elevation of the cyclic AMP level and suppression of the cytotoxicity. Theophylline did not increase the cyclic AMP concentration, but potentiated the effects of isoproterenol and prostaglandin E1 on the cyclic AMP levels, and significantly inhibited cytotoxicity. No clear effects were seen when cyclic GMP, dibutyryl GMP, acetylcholine or carbacholine were added to the cells. The results indicate that in this system cyclic AMP inhibits cytotoxicity, while no evidence for a role of cyclic GMP has been obtained.