Pretreatment with lipoteichoic acid sensitizes target cells to antibody-dependent cellular cytotoxicity in the presence of anti-lipoteichoic acid antibodies

Abstract

This study was performed to determine whether antibody-dependent cellular cytotoxicity (ADCC) could be directed against mammalian cells sensitized with spontaneously adhering bacterial substances. 51Cr-labeled SB leukemia cells were incubated with purified S43 group A streptococcal lipoteichoic acid (LTA; 0.001 to 100 micrograms/ml). Purified leukocyte ADCC effector cells were added to the LTA-coated target cells at various effector-to-target ratios (100:1 to 12:1), followed by the addition of rabbit anti-LTA. After incubation for 4 h, target cell lysis was calculated based on the release of label into the medium. As little as 1 ng of LTA per ml was sufficient to sensitize the target cells to ADCC lysis (12%); however, concentrations above 0.1 micrograms/ml generally resulted in 60 to 80% lysis. LTA alone was not cytotoxic to these target cells. Targeting did not occur if effector cells were sensitized or if free LTA was added to the medium. Specificity was demonstrated by cold-target inhibition, which showed that anti-LTA cytotoxicity could be inhibited only by unlabeled, LTA-treated target cells but not by cold SB cells alone. The findings indicate that certain soluble bacterial components, when bound to mammalian cells in the presence of specific antibody, can target ADCC effectors to these cells. This mechanism may be an important factor in the delayed sequelae of bacterial infections.