Simian Immunodeficiency Virus-Producing Cells in Follicles Are Partially Suppressed by CD8+ Cells In Vivo.
Folkvord, Joy M
Rakasz, Eva G
Abdelaal, Hadia M
Wagstaff, Reece K
Kovacs, Katalin J
Kim, Hyeon O
Skinner, Pamela J
AffiliationDivision of Infectious Diseases, University of Arizona
MetadataShow full item record
PublisherAMER SOC MICROBIOLOGY
CitationSimian Immunodeficiency Virus-Producing Cells in Follicles Are Partially Suppressed by CD8+ Cells In Vivo. 2016, 90 (24):11168-11180 J. Virol.
JournalJournal of Virology
RightsCopyright © 2016, American Society for Microbiology. All Rights Reserved.
Collection InformationThis 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 firstname.lastname@example.org.
AbstractHuman 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.
NoteAccepted manuscript posted online 5 October 2016; 6 month embargo.
VersionFinal accepted manuscript
SponsorsHHS | National Institutes of Health (NIH) [P51OD011106/P51RR000167, R01AI096966, R01AI090732, R56AI080418]
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