Blockade of virus infection by human CD4+ T cells via a cytokine relay network

Ann M. Davis, Kristan A. Hagan, Loderick A. Matthews, Gagan Bajwa, Michelle A. Gill, Michael Gale, J. David Farrar

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


CD4+ T cells directly participate in bacterial clearance through secretion of proinflammatory cytokines. Although viral clearance relies heavily on CD8+ T cell functions, we sought to determine whether human CD4+ T cells could also directly influence viral clearance through cytokine secretion. We found that IFN-γ and TNF-α, secreted by IL-12-polarized Th1 cells, displayed potent antiviral effects against a variety of viruses. IFN-γ and TNF-α acted directly to inhibit hepatitis C virus replication in an in vitro replicon system, and neutralization of both cytokines was required to block the antiviral activity that was secreted by Th1 cells. IFN-γ and TNF-α also exerted antiviral effects against vesicular stomatitis virus infection, but in this case, functional type I IFN receptor activity was required. Thus, in cases of vesicular stomatitis virus infection, the combination of IFN-γ and TNF-α secreted by human Th1 cells acted indirectly through the IFN-α/β receptor. These results highlight the importance of CD4+ T cells in directly regulating antiviral responses through proinflammatory cytokines acting in both a direct and indirect manner.

Original languageEnglish
Pages (from-to)6923-6932
Number of pages10
JournalJournal of Immunology
Issue number10
StatePublished - 2008


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