TY - JOUR
T1 - Blockade of virus infection by human CD4+ T cells via a cytokine relay network
AU - Davis, Ann M.
AU - Hagan, Kristan A.
AU - Matthews, Loderick A.
AU - Bajwa, Gagan
AU - Gill, Michelle A.
AU - Gale, Michael
AU - Farrar, J. David
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=45549097810&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.180.10.6923
DO - 10.4049/jimmunol.180.10.6923
M3 - Article
C2 - 18453613
AN - SCOPUS:45549097810
SN - 0022-1767
VL - 180
SP - 6923
EP - 6932
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -