Abstract
HIV replicates primarily in lymphoid tissue and immune activation is a major stimulus in vivo. To determine the cells responsible for HIV replication during Ag-driven T cell activation, we used a novel in vitro model employing dendritic cell presentation of superantigen to CD4(+) T cells. Dendritic cells and CD4(+) T cells are the major constituents of the paracortical region of lymphoid organs, the main site of Ag-specific activation and HIV replication. Unexpectedly, replication occurred in nonproliferating bystander CD4(+) T cells that lacked activation markers. In contrast, activated Ag-specific cells were relatively protected from infection, which was associated with CCR5 and CXC chemokine receptor 4 down-regulation. The finding that HIV replication is not restricted to highly activated Ag-specific CD4(+) T cells has implications for therapy, efforts to eradicate viral reservoirs, immune control of HIV, and Ag-specific immune defects.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antigen Presentation
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Bacterial Toxins*
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Biomarkers / blood
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism*
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CD4-Positive T-Lymphocytes / virology
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Cell Division / immunology
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Cells, Cultured
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Coculture Techniques
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Dendritic Cells / immunology
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Dendritic Cells / virology
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Enterotoxins / immunology
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Epitopes, T-Lymphocyte / immunology
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HIV-1 / immunology*
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Humans
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Interphase / immunology
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Lymphocyte Activation* / immunology
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Models, Immunological
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Receptors, HIV / biosynthesis
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Receptors, HIV / metabolism
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Staphylococcus aureus / immunology
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Superantigens / immunology
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism*
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T-Lymphocyte Subsets / virology
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Virus Replication / immunology*
Substances
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Bacterial Toxins
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Biomarkers
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Enterotoxins
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Epitopes, T-Lymphocyte
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Receptors, HIV
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Superantigens
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enterotoxin F, Staphylococcal