Participation of endogenous tumour necrosis factor in host resistance to cytomegalovirus infection

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Abstract
Interferon gamma (IFNγ) represents an essential cytokine involved in murine cytomegalovirus (MCMV) clearance from the salivary gland and the control of horizontal transmission. Because IFNγ cannot be responsible for all cytokine effects during recovery from MCMV infection we have now tested the potential participation of tumour necrosis factor alpha (TNFα) in the antiviral defence. Neutralization of endogenous TNFα abolished the antiviral activity of CD4 T cells in immunocompetent as well as in CD8 subset-deficient mice. These data suggest that the antiviral effect of the CD4 subset requires the presence of at least two cytokines, namely IFNγ and TNFα. Depletion of endogenous TNFα in adoptive cell transfer recipients diminished the antiviral function of CD8 T lymphocytes suggesting that TNFα also participates in CD8 T cell effector functions. Furthermore, endogenous cytokines were found to be required for survival after infection with lethal doses of MCMV, whereas immunotherapy with recombinant TNFα and IFNγ could not limit virus replication in vivo. The results suggest that, similar to IFNγ, TNFα is an integral part of the protective mechanisms involved in cytomegalovirus clearance.
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