Nonproliferating bystander CD4+ T cells lacking activation markers support HIV replication during immune activation

The Journal of Immunology : Official Journal of the American Association of Immunologists
D ScalesD Weissman

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.

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Citations

Apr 14, 2004·Proceedings of the National Academy of Sciences of the United States of America·Concepción MarañónAnne Hosmalin
Mar 24, 2007·Nature Reviews. Immunology·Oliver T FacklerOlivier Schwartz
Feb 21, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Audrey L KinterAnthony S Fauci
Oct 23, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·John CapodiciDrew Weissman
Feb 12, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jian DingTheresa L Chang
Jun 27, 2002·Proceedings of the National Academy of Sciences of the United States of America·Massimo AlfanoGuido Poli
Dec 6, 2006·Immunology and Cell Biology·M L Munier, A D Kelleher

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