The roles of perforin- and Fas-dependent cytotoxicity in protection against cytopathic and noncytopathic viruses.
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).
Kägi
D
D
Department of Pathology, University of Zürich, Switzerland.
Seiler
P
P
Pavlovic
J
J
Ledermann
B
B
Bürki
K
K
Zinkernagel
R M
RM
Hengartner
H
H
D018354:Alphavirus Infections / Q000276:immunology / Q000517:prevention & control; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D003588:Cytopathogenic Effect, Viral; D003602:Cytotoxicity, Immunologic; D007113:Immunity, Innate; D016219:Immunotherapy, Adoptive; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000517:prevention & control; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008562:Membrane Glycoproteins / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011994:Recombinant Proteins / Q000276:immunology; D012672:Semliki forest virus / Q000276:immunology; D014615:Vaccinia / Q000276:immunology / Q000517:prevention & control; D014616:Vaccinia virus / Q000276:immunology; D019014:fas Receptor / Q000633:toxicity*
D000914:Antibodies, Viral; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D011994:Recombinant Proteins; D019014:fas Receptor; D054353:Perforin