The role of apoptosis in antibody-dependent cellular cytotoxicity |
| |
Authors: | S John Curnow Martin J Glennie George T Stevenson |
| |
Institution: | (1) Lymphoma Research Unit, Tenovus Laboratory, General Hospital, SO9 4XY Southampton, UK;(2) Present address: Centre d'immunologie INSERM-CNRS de Marseille-Luminy, Parc Scientifique de Luminy, Case 906, 13 288 Marseille, Cedex 9, France |
| |
Abstract: | Apoptosis in three lymphoma cell lines has been studied following cytotoxicity induced in vitro by normal human blood lymphocytes utilizing either natural killer (NK) or antibody-dependent cellular cytotoxic (ADCC) mechanisms. Guinea-pig L2C leukaemic lymphocytes, but not the human cell lines Daudi and Jurkat, revealed a degree of time- and temperature-dependent apoptotic death upon simple culture in vitro. NK cytotoxicity at low effector: target ratios (E: T) induced both release of51Cr and apoptosis. However NK cytotoxicity at higher E : T, and ADCC at all E : T, increased the level of51Cr release while reducing the level of apoptosis. The findings were consistent with the apoptotic process being cut short by intervention of necrotic death. The same characteristics accompanied ADCC whether the effectors were recruited by Fc regions of antibody coating the targets, or by bispecific antibodies attaching one arm to the targets and the other to Fc receptors type III on effectors. This finding, and the high level of cytotoxicity elicited by the bispecific method, confirm the belief that NK cells, in addition to exerting NK cytotoxicity, represent the principal effectors for ADCC among blood mononuclear cells. Our results suggest that NK cells have both apoptotic and necrotic mechanisms available for killing their targets, but use only the latter for ADCC. |
| |
Keywords: | Apoptosis DNA fragmentation Cellular cytotoxicity NK cells |
本文献已被 SpringerLink 等数据库收录! |
|