Selectivity of inhibition by anticancer agents of mouse spleen immune effector functions involved in responses to sheep erythrocytes.

The selective effects of 24 agents on mouse spleen effector functions involved in the immune responses to sheep erythrocytes have been demonstrated. Five tests were used to assay the effector functions: the comple ment-dependent cellular cytotoxicity test, which mea sures complement-mediated lysis in the presence of anti body excreted from B-cell effectors; the complement-in dependent cellular cytotoxicity test, which measures lysis after non-T-cell, non-B-cell interactions with target cells coated with antibody excreted by B-cells within the same spleen cell populations; the antibody-dependent cellular cytotoxicity test, which measures lysis after non-T-cell, non-B-cell interactions with antiserum-coated target cells; the complement-independent phagocytic test and the an tibody-dependent phagocytic test, which measure phago cytosis of target cells coated with endogenous and added antibody, respectively. These five tests were, in general, insensitive to inhibitors of DNA synthesis. Phagocytosis and lysis associated with complement-independent cellu lar cytotoxicity were selectively sensitive to protein inhib itors, anthracycline antibiotics, bleomycin, actinomycin D, 2-deoxy-D-glucose, and Ne-benzyladenosine. All func tions, except complement-dependent cellular cytotoxicity, were inhibited by agents that affect cellular motility and/ or membrane characteristics. The complement-depend ent cellular cytotoxicity was only affected by agents that probably acted in a nonspecific cytotoxic manner. Potentiation of immune function was demonstrated in one case, namely, with A/6-(A2-isopentenyl)adenosine. The demon strated selectivity of action of the agents studied in vitro permitted speculation concerning the cellular effector functions involved in the efferent arm of the mouse spleen cell response to sheep erythrocytes and indicated selectivities on cellular functions that may become relevant in vivo.