The roles of perforin- and Fas-dependent cytotoxicity in protection against cytopathic and noncytopathic viruses

Eur J Immunol. 1995 Dec;25(12):3256-62. doi: 10.1002/eji.1830251209.


In vitro, T cell-dependent cytotoxicity is mediated by two distinct mechanisms, one being perforin-, the other Fas-dependent. The contribution of both of these mechanisms to clearance of viral infections was investigated in mice for the non-cytopathic lymphocytic choriomeningitis virus (LCMV) and the cytopathic vaccinia, vesicular stomatitis (VSV) and Semliki forest (SFV) viruses. Clearance of an acute LCMV infection was mediated by the perforin-dependent mechanism without measurable involvement of the Fas-dependent pathway. For the resolution of vaccinia virus infection and for resistance against VSV and SFV, however, neither of the two pathways was required. These data suggest that perforin-dependent cytotoxicity mediated by T cells is crucial for protection against non-cytopathic viruses, whereas infections with cytopathic viruses are controlled by nonlytic T cell-dependent soluble mediators such as cytokines (IFN-gamma against vaccinia virus) and neutralizing antibodies (against VSV and SFV).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alphavirus Infections / immunology
  • Alphavirus Infections / prevention & control
  • Animals
  • Antibodies, Viral / biosynthesis
  • Cytopathogenic Effect, Viral*
  • Cytotoxicity, Immunologic*
  • Immunity, Innate
  • Immunotherapy, Adoptive
  • Lymphocytic Choriomeningitis / immunology
  • Lymphocytic Choriomeningitis / prevention & control
  • Lymphocytic choriomeningitis virus / immunology
  • Membrane Glycoproteins / toxicity*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • Recombinant Proteins / immunology
  • Semliki forest virus / immunology
  • Vaccinia / immunology
  • Vaccinia / prevention & control
  • Vaccinia virus / immunology
  • fas Receptor / toxicity*


  • Antibodies, Viral
  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • Recombinant Proteins
  • fas Receptor
  • Perforin