Spontaneous and antibody-dependent cellular cytotoxicity in melanoma patients and healthy control presons
Peter, H.H.; Knoop, F.; Kalden, J.R.
Zeitschrift für Immunitatsforschung Experimentelle und Klinische Immunologie 151(3): 263-281
1976
ISSN/ISBN: 0300-872X PMID: 134545 Document Number: 109029
Spontaneous cell mediated cytotoxicity (SCMC) and antibody dependent cellular cytotoxicity (ADCC) against 51Cr labeled allogeneic target cells of a human melanoma cell line (IGR 3) were determined with purified effector lymphocytes and defibrinated whole blood from 14 melanoma patients and 13 healthy control persons. Peripheral blood lymphocytes were isolated by Ficoll gradient centrifugation (fraction F). Subsequently the phagocytic and adherent cells were removed and the supernatant cell population (fraction FFF) was passaged through IgG [immunoglobulin G] anti-IgG columns to obtain a B [bone marrow-derived] cell free lymphocyte suspension (fraction FFF-C). Cells from the 3 lymphocyte fractions and defibrinated whole blood were simultaneously tested for cytotoxic activity against unsensitized IGR 3 target cells (SCMC assay) and IGR 3 cells previously sensitized with rabbit anti-melanoma IgG (ADCC assay). Dose-response curves were established with all lymphocyte fractions and whole blood. With all lymphocyte fractions tested, ADCC was approximately 15 times higher than SCMC; with whole blood, the difference tended to be less pronounced. Elimination of phagocytic and adherent cells had no significant effect on SCMC and ADCC. Passage over IgG anti-IgG columns drastically reduced cytotoxicity in both assays without completely abolishing it. The only difference seen between lymphocyte cytotoxicity of melanoma patients and control persons was a slight, but non significant depression of SCMC and ADCC in melanoma patients. The results confirm and extend the previous report that SCMC against an allogeneic tumor cell line is due to non specific null or K cell-activity rather than to specific T [thymus-derived] cell cytotoxicity. In 1 experiment freshly explanted melanoma cells were labeled with 51Cr and reacted with antologous blood and purified lymphocyte fractions. Cellular cytotoxicity depending on serum factors (ADCC) was an effective lytic mechanism; T cell mediated cytotoxicity could not be demonstrated.