Cytolysis of Adenovirus-Infected Murine Fibroblasts by IFN-γ-Primed Macrophages Is TNF- and Contact-Dependent

Abstract

The effect of interferon-γ (IFN-γ) priming on macrophages for cytolysis of adenovirus-infected murine fibroblasts was examined using peritoneal macrophages and the RAW264.7 (RAW) murine macrophage cell line. Adenovirus-infected cells were lysed by IFN-γ-primed RAW macrophages via a TNF- and contact-dependent mechanism under conditions in which little or no soluble TNF was detected in the supernatant of these effectors. TNF involvement in the lytic mechanism of IFN-γ-primed macrophages is shown by (a) cytolysis of TNF-sensitive LM and adenovirus E1A-expressing cells, (b) protection from cytolysis by the adenovirus E3-14.7K protein and the E3-10.4/14.5K complex of proteins, and (c) inhibition of cytolysis when neutralizing anti-TNF serum is added to cocultures of macrophages and susceptible adenovirus-infected targets. Physical separation of effectors and targets prevents cytolysis, indicating that cell contact is required. Nonetheless, IFN-γ-primed RAW macrophages are unable to lyse E8 tumor cells, which are killed by fully activated (triggered) macrophages. These findings indicate that IFN-γ-primed macrophages are cytolytic for TNF-sensitive targets without soluble TNF release, but they lack the full cytolytic capacity of LPS-triggered macrophages.