Nonproliferating bystander CD4+ T cells lacking activation markers support HIV replication during immune activation.
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.
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Division of Infectious Diseases and Center for AIDS Research, University of Pennsylvania, Philadelphia, PA 19104, USA.
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Shaheen
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Capodici
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Cannon
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Weissman
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D017951:Antigen Presentation; D001427:Bacterial Toxins; D015415:Biomarkers / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D004768:Enterotoxins / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007399:Interphase / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D018448:Models, Immunological; D015728:Receptors, HIV / Q000096:biosynthesis / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D014779:Virus Replication / Q000276:immunology*
D001427:Bacterial Toxins; D015415:Biomarkers; D004768:Enterotoxins; D018984:Epitopes, T-Lymphocyte; D015728:Receptors, HIV; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal