Anti-HIV state but not apoptosis depends on IFN signature in CD4+ T cells

A Audigé, M Urosevic, E Schlaepfer… - The Journal of …, 2006 - journals.aai.org
A Audigé, M Urosevic, E Schlaepfer, R Walker, D Powell, S Hallenberger, H Joller…
The Journal of Immunology, 2006journals.aai.org
To gain insights into the molecular mechanisms underlying early host responses to HIV in
the CD4+ T cell target population, we examined gene expression in CD4+ T cells isolated
24 h after ex vivo HIV infection of lymphocyte aggregate cultures derived from human tonsils.
Gene profiling showed a distinct up-regulation of genes related to immune response and
response to virus, notably of IFN-stimulated genes (ISGs), irrespective of the coreceptor
tropism of the virus. This mostly IFN-α-dependent gene signature suggested the involvement …
Abstract
To gain insights into the molecular mechanisms underlying early host responses to HIV in the CD4+ T cell target population, we examined gene expression in CD4+ T cells isolated 24 h after ex vivo HIV infection of lymphocyte aggregate cultures derived from human tonsils. Gene profiling showed a distinct up-regulation of genes related to immune response and response to virus, notably of IFN-stimulated genes (ISGs), irrespective of the coreceptor tropism of the virus. This mostly IFN-α-dependent gene signature suggested the involvement of plasmacytoid dendritic cells, a principal component of the antiviral immune response. Indeed, depletion of plasmacytoid dendritic cells before HIV inoculation abrogated transcriptional up-regulation of several ISGs and resulted in increased levels of HIV replication. Treatment with a blocking anti-IFN-αR Ab yielded increased HIV replication; conversely, HIV replication was decreased in pDC-depleted cultures treated with IFN-α. Among up-regulated ISGs was also TRAIL, indicating a potential role of the IFN signature in apoptosis. However, a blocking anti-TRAIL Ab did not abrogate apoptosis of CD4+ T cells in CXCR4-tropic HIV-infected cultures, suggesting the involvement of pathways other than TRAIL mediated. We conclude that acute HIV infection of lymphoid tissue results in up-regulation of ISGs in CD4+ T cells, which induces an anti-HIV state but not apoptosis.
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