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, but Not Tumour Necrosis Factor 
, Displays Antiviral Activity in vivo
Division of Virology, Department of Neuropharmacology, Research Institute of Scripps Clinic, 10666 N. Torrey Pines Road, La Jolla, California 92037, U.S.A.
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-
) and tumour necrosis factor (TNF
) in virus clearance. In vitro the amount of IFN- 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- 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- 24 h before or at the same time as virus inoculation showed reduced virus titres in their spleens. Hence, IFN- displayed a direct antiviral effect in vivo. In contrast, treatment of mice with recombinant TNF had no effect on virus clearance and thus TNF is unlikely to play a significant role in this acute viral infection.
Keywords: CTL, cytolysis, clearance, interferon, tumour necrosis factor
Present address: Roche Products Limited, Department of Chemotherapy Biology, P.O. Box 8, Welwyn Garden City, Hertfordshire AL7 3AY, U.K.
Received 15 August 1989;
accepted 30 August 1989.
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