Role of oxygen-dependent mechanisms in monoclonal antibody-induced lysis of normal T cells by phagocytes: I. — Human phagocytes

Abstract

The present study investigates the lytic potential of the reactive oxygen species (ROS) which, as previously shown in our laboratory, are generated within the first minutes following the Fc-receptor-mediated interaction between phagocytic cells and anti-T-cell monoclonal-antibody (mAb)-coated T lymphocytes. A comparative study of ROS production (measured by chemiluminescence (CL] and the cytotoxic effect (evaluated in a 51Cr release antibody-dependent cellular cytotoxicity (ADCC) assay) of human polymorphonuclear (PMN) and mononuclear (MN) cells against mAb-coated autologous, allogeneic and xenogeneic (murine) thymocytes showed that the two reactions were closely interdependent for PMN and co-existed without significant correlation for MN cells. Catalase and superoxide dismutase did not modify ADCC results, suggesting that these ROS scavengers could not diffuse into the target cell destruction area. Colchicine treatment of PMN and MN cells at a dose inhibiting phagocytosis consistently impaired their CL generation and, in parallel, strongly reduced PMN-mediated ADCC but only weakly reduced that of MN cells. PMN and MN cells from 14 patients with chronic granulomatous disease (CGD) were not capable of producing CL after contact with mAb-coated T cells and showed significantly reduced ADCC activities, while PMN and MN cells from mothers carrying the X-linked type of CGD exhibited ADCC and oxidative responses of an intermediate level. We conclude that ADCC mediated by human PMN cells against T cells is mainly dependent upon the generation of ROS, whereas that induced by MN cells is most likely effected by both oxidative and non-oxidative events.