Human polymorphonuclear leukocyte-mediated cytotoxicity against varicella-zoster virus-infected fibroblasts

Abstract

Polymorphonuclear leukocytes (PMN) were studied for their ability to mediate cytotoxicity against varicella-zoster virus (VZV)-infected and uninfected human fibroblasts in 51Cr release assays. PMN were capable of mediating antibody-dependent cellular cytotoxicity (ADCC) against VZV-infected targets. Maximal ADCC was obtained with effector-to-target ratios of 100:1 and 18 h of incubation. Percent 51Cr release for 26 normal adults was 14.1 +/- 0.6 (mean +/- standard error) in the presence of pooled human seropositive sera (final dilution, 1:100) and 0.5 +/- 0.6 in the presence of pooled human seronegative sera. Addition of phorbol myristate acetate (PMA) enhanced PMN-mediated cytotoxicity against VZV-infected and uninfected targets. PMA-stimulated cytotoxicity was optimal with PMA concentrations of 200 ng/ml and effector-to-target ratios of 10:1, and antibody was not required; killing was detected as early as 3 h after incubation and was maximal after 18 h. Highly purified PMN were capable of mediating both ADCC and PMA-stimulated lysis. Catalase completely inhibited PMA-stimulated PMN cytotoxicity, but had no effect on PMN-mediated ADCC. PMN from patients with chronic granulomatous disease were capable of mediating ADCC, but not PMA-stimulated killing, against VZV-infected targets. Thus, PMN could kill VZV-infected targets by two different mechanisms: ADCC, which required antibody but not hydrogen peroxide (H2O2), and PMA-stimulated cytotoxicity, which required H2O2 but not antibody.