Inhibition of natural, interleukin-2 stimulated and bacillus Calmette-Guerin enhanced cytotoxicity with anti-CD16 antibodies.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Kaasinen
Eero S
ES
Hyvinkää Hospital, Hyvinkää, Haartman Institute, Department of Pathology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
Harju
Leena M
LM
Timonen
Tuomo T
TT
D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000187:drug effects; D001500:BCG Vaccine / Q000494:pharmacology*; D002295:Carcinoma, Transitional Cell / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000276:immunology*; D001749:Urinary Bladder Neoplasms / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D001500:BCG Vaccine; D007376:Interleukin-2; D017452:Receptors, IgG; D015375:Receptors, Interleukin-2