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

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-gamma and TNF-alpha, secreted by IL-12-polarized Th1 cells, displayed potent antiviral effects against a variety of viruses. IFN-gamma and TNF-alpha 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-gamma and TNF-alpha 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-gamma and TNF-alpha secreted by human Th1 cells acted indirectly through the IFN-alpha/beta 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.

• Authors: Ann M Davis, Kristan A Hagan, Loderick A Matthews, Gagan Bajwa, Michelle A Gill, Michael Gale Jr, J David Farrar
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 180 Issue 10 Pg. 6923-32 (May 15 2008) ISSN: 0022-1767 [Print] United States
• PMID: 18453613 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cytokines
• Tumor Necrosis Factor-alpha
• Interleukin-12
• Interferon-gamma

Topics

• Blotting, Western
• Cytokines (immunology, metabolism)
• Enzyme-Linked Immunosorbent Assay
• Hepacivirus (immunology, physiology)
• Humans
• Interferon-gamma (immunology, metabolism)
• Interleukin-12 (immunology)
• Lymphocyte Activation (immunology)
• Th1 Cells (immunology)
• Tumor Necrosis Factor-alpha (immunology, metabolism)
• Vesicular stomatitis Indiana virus (immunology)
• Virus Diseases (immunology)
• Virus Replication