Apparent direct cellular cytotoxicity mediated via cytophilic antibody. Multiple Fc receptor bearing effector cell populations mediating cytophilic antibody induced cytotoxicity.

Guinea-pigs immunized with chicken red blood cells (CRBC) developed cytotoxic effector cells in peripheral blood, spleen, lymph nodes, bone marrow and peritoneal exudate cells. Although it appeared that direct cytotoxicity was the mechanism of killing in this model, the true mechanism of cytotoxicity was in fact cytophilic antibody firmly bound to the effector cell rendering it specifically cytotoxic to the CRBC targets. Using multiple cell separation procedures, we demonstrated at least three distinct effector cell populations capable of mediating cytotoxicity in this model: a monocyte-macrophage, a non-phagocytic lymphocyte and a neutrophil, all bearing Fc receptors for Ig. Cell free eluates produced from immune effector cells were capable of rendering non-immune cells of all three Fc receptor bearing leucocyte classes cytotoxic. It is noteworthy that several techniques commonly employed to deplete effector cell populations were shown also to remove cytophilic antibody from the surface of these effector cells. If this had not been recognized, the cytophilic antibody component of the system would have been overlooked and erroneous conclusions would have been made as to which cell populations were functioning as effectors. Recent clinical studies have demonstrated a direct cytotoxicity by K lymphocytes—the usual effector cells in antibody dependent cellular cytotoxicity. The present study suggests that in at least some of these cases true direct cytotoxicity may not be the mechanism of killing and that K cells bearing cytophilic antibody may in fact be the effector cell operating by antibody dependent cellular cytotoxicity.