Anti-HIV state but not apoptosis depends on IFN signature in CD4+ T cells
| Autor: | Doug Powell, Erika Schlaepfer, Reinhard Dummer, Roberto F. Speck, Mirjana Urosevic, Helen Joller, Hans-Uwe Simon, Sabine Hallenberger, Russell M. Walker, Annette Audigé |
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| Rok vydání: | 2006 |
| Předmět: |
CD4-Positive T-Lymphocytes
T cell Lymphocyte Immunology Palatine Tonsil Apoptosis Biology Virus Replication Virus TNF-Related Apoptosis-Inducing Ligand Immune system medicine Immunology and Allergy Humans Antibodies Blocking Gene Gene Expression Profiling Immunity virus diseases HIV Interferon-alpha Dendritic Cells Gene signature Virology Up-Regulation Lymphatic system medicine.anatomical_structure Interferons |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 177(9) |
| ISSN: | 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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