THE ROLES OF PERFORIN-DEPENDENT AND FAS-DEPENDENT CYTOTOXICITY IN PROTECTION AGAINST CYTOPATHIC AND NONCYTOPATHIC VIRUSES

In vitro, T cell-dependent cytotoxicity is mediated by two distinct me chanisms, one being perforin-, the other Fas-dependent. The contributi on of both of these mechanisms to clearance of viral infections was in vestigated in mice for the noncytopathic lymphocytic choriomeningitis virus (LCMV) and the cytopathic vaccinia, vesicular stomatitis (VSV) a nd Semliki forest (SFV) viruses. Clearance of an acute LCMV infection was mediated by the perforin-dependent mechanism without measurable in volvement of the Pas-dependent pathway. For the resolution of vaccinia virus infection and for resistance against VSV and SFV, however, neit her of the two pathways was required. These data suggest that perforin -dependent cytotoxicity mediated by T cells is crucial for protection against noncytopathic viruses, whereas infections with cytopathic viru ses are controlled by nonlytic T cell-dependent soluble mediators such as cytokines (IFN-gamma against vaccinia virus) and neutralizing anti bodies (against VSV and SFV).