Inhibition Of Natural, Interleukin-2 Stimulated and Bacillus Calmette-Guerin Enhanced Cytotoxicity With Anti-CD16 Antibodies

Abstract

We studied the cytolytic mechanism of nonstimulated, bacillus Calmette-Guerin (BCG) stimulated and interleukin (IL)-2 (Chiron Corp., Amsterdam, The Netherlands) stimulated peripheral blood mononuclear cells. We inhibited the cytotoxicity of nonstimulated, BCG stimulated and IL-2 stimulated peripheral blood mononuclear cells against various target cells using 3 monoclonal antibodies directed against the CD16 receptor of natural killer cells or alternatively monoclonal antibodies against the alpha and beta subunits of the IL-2 receptor complex (IL-2R). The main target cell was the poorly differentiated transitional cell line T24. Of the 3 anti-CD16 antibodies tested only CLB FcR-gran/1 effectively inhibited natural, IL-2 stimulated and BCG enhanced cytotoxicity. Cytotoxicity was also markedly diminished after depletion of CD16+CD56+/- cells with CLB FcR-gran/1. An hour of pretreatment with CLB FcR-gran/1 was enough to reduce significantly the level of cytotoxicity evoked by overnight stimulation with BCG or IL-2. Simultaneous administration of anti-IL-2Ralpha and anti-IL-2Rbeta significantly decreased the killing of target cells by BCG stimulated and IL-2 stimulated peripheral blood mononuclear cells. Within the stimulation times chosen the same killing mechanisms seemed to explain the nonstimulated, BCG stimulated and IL-2 stimulated cytotoxicity with CD16 positive cells as central effectors. Anti-CD16 antibodies may deliver a target cell independent down-regulatory signal to natural killer cells or alternatively mimic a nonIg ligand and block the detection of the target cell.