Mechanism of recovery from acute virus infection. VIII. Treatment of lymphocytic choriomeningitis virus-infected mice with anti-interferon-gamma monoclonal antibody blocks generation of virus-specific cytotoxic T lymphocytes and virus elimination.
In acutely infected mice the lymphocytic choriomeningitis (LCM) virus multiplies to high titers in essentially all tissues. Around day 6, virus clearance sets in, which has previously been shown to be mediated by CD8+ cytotoxic T lymphocytes (CTL), probably by releasing (or inducing other cells to release) anti-viral cytokines. To ascertain whether interferon-gamma plays a role, infected mice were injected once i.v. with monoclonal antibody known to neutralize this lymphokine, and the effect this had on both termination of the infection and development of LCM virus-specific CTL was determined. Administration 1 day after infection blocked virus elimination from spleen and liver and decreased the generation of CTL; also, limiting dilution analysis revealed absence of activation of CTL precursors. In contrast, when the antibody was given 3 days after or 1 day before the virus, neither clearance nor generation of CTL was measurably affected. Furthermore, the antiviral effect of immune spleen cells after their transfer into infected recipients was not altered by treatment of the latter with monoclonal antibody. We conclude that in the generation of LCM virus-specific CTL an early event is dependent on constitutively produced interferon-gamma; when its activity is blocked, CTL do not mature, resulting in the mouse's inability to terminate the infection.
Wille
A
A
Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, Universität Hamburg, FRG.
Gessner
A
A
Lother
H
H
Lehmann-Grube
F
F
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics; D000937:Antigen-Antibody Reactions; D007111:Immunity, Cellular; D007116:Immunization, Passive; D007371:Interferon-gamma / Q000502:physiology*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007371:Interferon-gamma