APPARENT DIRECT CELLULAR CYTOTOXICITY MEDIATED VIA CYTOPHILIC ANTIBODY - MULTIPLE FC RECEPTOR BEARING EFFECTOR CELL-POPULATIONS MEDIATING CYTOPHILIC ANTIBODY INDUCED CYTOTOXICITY

Abstract

Guinea-pigs immumized 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, at least 3 distinct effector cell populations were demonstrated which were capable of mediating cytotoxicity in this model: a monocyte-macrophage, a non-phagocytic lymphocyte and a neutrophil, all bearing Fc receptors for Ig [immunoglobulin]. Cell free eluates produced from immune effector cells were capable of rendering non-immune cells of all 3 Fc receptors bearing leukocyte classes cytotoxic. Several techniques commonly employed to deplete effector cell populations removed cytophilic antibody from the surface of these effector cells. If this were not 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 demonstrated a direct cytotoxicity by K [antibody-dependent killer] lymphocytes. In at least some of these cases true direct cytotoxicity may not be the mechanism of killing. K cells bearing cytophilic antibody may be the effector cell operating by antibody dependent cellular cytotoxicity.