Role of oxygen-dependent mechanisms in monoclonal-antibody-induced lysis of normal T cells by phagocytes. II. Murine phagocytes.
In the first part of this study, we reported that antibody-dependent cellular cytotoxicity (ADCC) mediated by human polymorphonuclear (PMN) and mononuclear (MN) phagocytes against anti-T-cell monoclonal-antibody-(mAb)-coated T lymphocytes, is mainly dependent upon the generation of reactive oxygen intermediates (ROI) for PMN, whereas MN-mediated ADCC depends on both oxidative and non-oxidative cytolytic events. Using mouse effector cells from various organs and at various maturation or activation states, the present report shows that in this ADCC model against mAb-coated normal T cells, resident spleen (SPC) and peritoneal exudate (PEC) cells selectively bound and developed oxidative responses to these mAb-coated normal target cells but remained ineffective in ADCC. Similar data were obtained with inflammatory recruited (thioglycollate-elicited or Biogel granuloma-induced) macrophages, whereas immunologically activated macrophages (from BCG-treated mice) mediated both strong oxidative responses and potent ADCC reactions. In contrast, and as in the human system, both resident (from bone marrow) and inflammatory PMN phagocytes exerted significant lysis of these mAb-sensitized normal lymphoid cells. These findings, which are similar to those reported in ADCC against tumour target cells, strongly suggest that the nature (normal or tumoral) of the target cell does not influence the lytic mechanisms of macrophage-mediated ADCC and that these latter require activated macrophages and, like PMN, involve strong (if not exclusive) ROI participation.
Descamps-Latscha
B
B
INSERM U 25 and CNRS UA 122, Hôpital Necker, Paris.
Golub
R M
RM
Nguyen
A T
AT
D000818:Animals; D000911:Antibodies, Monoclonal; D000920:Antibody-Dependent Cell Cytotoxicity; D005260:Female; D006099:Granuloma / Q000276:immunology; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D051379:Mice; D008811:Mice, Inbred DBA; D009163:Mycobacterium bovis / Q000276:immunology; D010100:Oxygen / Q000378:metabolism*; D010586:Phagocytes / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D006861:Hydrogen Peroxide; D010100:Oxygen