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 journalArticle

13 Citations (Scopus)

Abstract

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 (US)
Pages (from-to)6923-6932
Number of pages10
JournalJournal of Immunology
Volume180
Issue number10
StatePublished - 2008

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Virus Diseases
Th1 Cells
Antiviral Agents
Cytokines
T-Lymphocytes
Vesicular Stomatitis
Replicon
Interleukin-12
Virus Replication
Hepacivirus
Viruses

ASJC Scopus subject areas

  • Immunology

Cite this

Davis, A. M., Hagan, K. A., Matthews, L. A., Bajwa, G., Gill, M. A., Gale, M., & Farrar, J. D. (2008). Blockade of virus infection by human CD4 + T cells via a cytokine relay network. Journal of Immunology, 180(10), 6923-6932.

Blockade of virus infection by human CD4 + T cells via a cytokine relay network. / Davis, Ann M.; Hagan, Kristan A.; Matthews, Loderick A.; Bajwa, Gagan; Gill, Michelle A.; Gale, Michael; Farrar, J. David.

In: Journal of Immunology, Vol. 180, No. 10, 2008, p. 6923-6932.

Research output: Contribution to journalArticle

Davis, AM, Hagan, KA, Matthews, LA, Bajwa, G, Gill, MA, Gale, M & Farrar, JD 2008, 'Blockade of virus infection by human CD4 + T cells via a cytokine relay network', Journal of Immunology, vol. 180, no. 10, pp. 6923-6932.
Davis AM, Hagan KA, Matthews LA, Bajwa G, Gill MA, Gale M et al. Blockade of virus infection by human CD4 + T cells via a cytokine relay network. Journal of Immunology. 2008;180(10):6923-6932.
Davis, Ann M. ; Hagan, Kristan A. ; Matthews, Loderick A. ; Bajwa, Gagan ; Gill, Michelle A. ; Gale, Michael ; Farrar, J. David. / Blockade of virus infection by human CD4 + T cells via a cytokine relay network. In: Journal of Immunology. 2008 ; Vol. 180, No. 10. pp. 6923-6932.
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