Cytotoxic T lymphocyte control of acute lymphocytic choriomeningitis virus infection: interferon gamma, but not tumour necrosis factor alpha, displays antiviral activity in vivo.
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-gamma) and tumour necrosis factor (TNF alpha) in virus clearance. In vitro the amount of IFN-gamma 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-gamma 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-gamma 24 h before or at the same time as virus inoculation showed reduced virus titres in their spleens. Hence, IFN-gamma displayed a direct antiviral effect in vivo. In contrast, treatment of mice with recombinant TNF alpha had no effect on virus clearance and thus TNF alpha is unlikely to play a significant role in this acute viral infection.
Klavinskis
L S
LS
Department of Neuropharmacology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Geckeler
R
R
Oldstone
M B
MB
D000208:Acute Disease; D000818:Animals; D002999:Clone Cells; D007111:Immunity, Cellular; D007116:Immunization, Passive; D007371:Interferon-gamma / Q000276:immunology*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D013154:Spleen / Q000382:microbiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma