Complement potentiation of phagocyte-mediated ADCC of HSV-infected corneal cells

Abstract

The authors have shown previously that rabbit alveolar macrophages, peritoneal exudate macrophages, and polymorphonuclear leukocytes are highly effective mediators of antibody-dependent cellular cytotoxicity (ADCC) against herpes simplex virus (HSV)-infected rabbit stromal keratocytes. Using a completely homologous system of nonimmune rabbit phagocytes, anti-HSV serum, complement, and HSV-infected stromal keratocyte targets, the authors have found significant potentiation of ADCC by complement. Lymphocyte-mediated ADCC, on the other hand, was not potentiated by complement. Using a 1:100 dilution of complement (noncytolytic in antibody-mediated lysis) and a 1:10 dilution of antiserum obtained from rabbits undergoing stromal keratitis, ADCC mediated by the three phagocytic cell types was augmented by approximately 22%. For example, using alveolar macrophages as effector cells, the addition of complement increased the level of ADCC From 40% to 60%, a 20% increase. Percent ADCC was augmented less by complement at higher antiserum dilutions. However, the percent of the total ADCC attributable to complement potentiation increased at these higher antiserum dilutions. In some cases, ADCC was not detectable at these high antiserum dilutions without the added complement. The potentiating effect was observed at complement dilutions as high as 1:400. Further dilution or heat-inactivation resulted in ADCC values comparable to those obtained without complement. Target cells exposed to complement alone were not killed by phagocytes.