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    Simian Immunodeficiency Virus-Producing Cells in Follicles Are Partially Suppressed by CD8+ Cells In Vivo.

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    Name:
    Li J Virol Follicular SIV-specific ...
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    5.775Mb
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    Description:
    Final Accepted Manuscript
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    Author
    Li, Shengbin
    Folkvord, Joy M
    Rakasz, Eva G
    Abdelaal, Hadia M
    Wagstaff, Reece K
    Kovacs, Katalin J
    Kim, Hyeon O
    Sawahata, Ryoko
    MaWhinney, Samantha
    Masopust, David
    Connick, Elizabeth
    Skinner, Pamela J
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    Affiliation
    Division of Infectious Diseases, University of Arizona
    Issue Date
    2016-12-15
    
    Metadata
    Show full item record
    Publisher
    AMER SOC MICROBIOLOGY
    Citation
    Simian Immunodeficiency Virus-Producing Cells in Follicles Are Partially Suppressed by CD8+ Cells In Vivo. 2016, 90 (24):11168-11180 J. Virol.
    Journal
    Journal of Virology
    Rights
    Copyright © 2016, American Society for Microbiology. All Rights Reserved.
    Collection Information
    This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
    Abstract
    Human immunodeficiency virus (HIV)- and simian immunodeficiency virus (SIV)-specific CD8(+) T cells are typically largely excluded from lymphoid B cell follicles, where HIV- and SIV-producing cells are most highly concentrated, indicating that B cell follicles are somewhat of an immunoprivileged site. To gain insights into virus-specific follicular CD8(+) T cells, we determined the location and phenotype of follicular SIV-specific CD8(+) T cells in situ, the local relationship of these cells to Foxp3(+) cells, and the effects of CD8 depletion on levels of follicular SIV-producing cells in chronically SIV-infected rhesus macaques. We found that follicular SIV-specific CD8(+) T cells were able to migrate throughout follicular areas, including germinal centers. Many expressed PD-1, indicating that they may have been exhausted. A small subset was in direct contact with and likely inhibited by Foxp3(+) cells, and a few were themselves Foxp3(+) In addition, subsets of follicular SIV-specific CD8(+) T cells expressed low to medium levels of perforin, and subsets were activated and proliferating. Importantly, after CD8 depletion, the number of SIV-producing cells increased in B cell follicles and extrafollicular areas, suggesting that follicular and extrafollicular CD8(+) T cells have a suppressive effect on SIV replication. Taken together, these results suggest that during chronic SIV infection, despite high levels of exhaustion and likely inhibition by Foxp3(+) cells, a subset of follicular SIV-specific CD8(+) T cells are functional and suppress viral replication in vivo These findings support HIV cure strategies that augment functional follicular virus-specific CD8(+) T cells to enhance viral control.
    Note
    Accepted manuscript posted online 5 October 2016; 6 month embargo.
    ISSN
    1098-5514
    PubMed ID
    27707919
    DOI
    10.1128/JVI.01332-16
    Version
    Final accepted manuscript
    Sponsors
    HHS | National Institutes of Health (NIH) [P51OD011106/P51RR000167, R01AI096966, R01AI090732, R56AI080418]
    ae974a485f413a2113503eed53cd6c53
    10.1128/JVI.01332-16
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