The antiviral activity of immune CD8+ T cells is dependent on interferon-gamma.
Vaccinia virus (VV) is a cytopathic virus that in normal mice exhibits only low virulence. However, when mice were treated throughout the course of the infection with mAb to IFN-gamma, the virus was lethal. The inability of these mice to clear the infection was not due to inhibition of effector T cell development since equally high numbers of cytotoxic T cells were generated in mAb- or control-treated mice. Instead, the data presented show that the defect was at the level of effector T cell activity. When immune CD8+ T cells were transferred to virus-infected recipients the infection was readily cleared. In contrast, effector cell function was totally blocked in mAb-treated recipients. We have considered these findings in view of our earlier observations that T cell deficient mice were able to resolve an otherwise lethal vv infection if infected with recombinant vv that encoded the genes for IL-2 or IFN-gamma. We propose a unifying concept such that antiviral T cells, which recognize infected cells in the context of class I MHC molecules, act to focus antiviral cytokines at the site of virus infection.
Ruby
J
J
Division of Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra.
Ramshaw
I
I
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D016827:CD8 Antigens / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D014615:Vaccinia / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016827:CD8 Antigens; D007371:Interferon-gamma