Cytotoxic T Lymphocyte Control of Acute Lymphocytic Choriomeningitis Virus Infection: Interferon , but Not Tumour Necrosis Factor , Displays Antiviral Activity in vivo

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Abstract
Summary Virus-specific cytotoxic T lymphocytes (CTL) mediate their antiviral activity either by direct lysis of infected cells, or by the release of soluble lymphokines, or by a combination of the two. We have examined the role played by interferon-gamma (IFN-γ) and tumour necrosis factor (TNFα) in virus clearance. In vitro the amount of IFN-γ synthesized by some lymphocytic choriomeningitis virus-specific H-2-restricted CTL clones was quantitatively too small to correlate with a direct antiviral activity in vivo. However, treatment of mice with a neutralizing monoclonal antibody to IFN-γ significantly inhibited the clearance of virus from the spleens of acutely infected mice given adoptive transfers of immune spleen cells. Additionally, mice treated with exogenous recombinant murine IFN-γ 24 h before or at the same time as virus inoculation showed reduced virus titres in their spleens. Hence, IFN-γ displayed a direct antiviral effect in vivo. In contrast, treatment of mice with recombinant TNFα had no effect on virus clearance and thus TNFα is unlikely to play a significant role in this acute viral infection.

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