Modulation of NK and K cell activity by trypsin treatment of effector cells

The effect of trypsin-treated human peripheral blood lymphocytes on spontaneous cell-mediated cytotoxicity (SCMC) and antibody-dependent cellular cytotoxicity (ADCC) was investigated using benzylpenicilloyl (BPO)-coated HeLa cells as targets. For ADCC-experiments an anti-BPO-IgG was purified from rabbit hyperimmune sera by affinity and subsequent ion exchange chromatography and used in different concentrations. After treatment of lymphocytes with high enzyme concentrations (21,500 U/2 X 10(6) lymphocytes/ml) both SCMC (mediated by NK cells) and ADCC (mediated by K cells) were markedly reduced in 3 hours as well as 18 hours 51Cr-release assays. Since decrease of K cell activity in this kind of assay might be due to impairment of SCMC, the effect of trypsin treatment was reevaluated in an NK-free system using BPO-coated lymphocytes as target cells and lymphocytes from the same donor as effector cells. Once again, in this system the K-cell activity was significantly reduced. Chessboard titration resulted in either enhancement of depression of ADCC depending on the dose of enzyme and IgG concentrations. In addition it could be seen from these dose response studies with different IgG concentrations (10--10,000 ng/ml) and different proteolytic activities (170--21,500 U/2 X 10(6) lymphocytes/ml) that the use of high IgG concentrations and low proteolytic activities might simulate resistance of K cells to trypsin treatment. The data presented indicate that the IgG-mediated ADCC should no longer be designated as "trypsin-resistant".