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Follicular regulatory T cells impair follicular T helper cells in HIV and SIV infection

Brodie Miles, Shannon M. Miller, Joy M. Folkvord, Abigail Kimball, Mastooreh Chamanian, Amie L. Meditz, Tessa Arends, Martin D. McCarter, David N. Levy, Eva G. Rakasz, Pamela J. Skinner and Elizabeth Connick ()
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Brodie Miles: Anschutz Medical Campus, University of Colorado
Shannon M. Miller: Anschutz Medical Campus, University of Colorado
Joy M. Folkvord: Anschutz Medical Campus, University of Colorado
Abigail Kimball: Anschutz Medical Campus, University of Colorado
Mastooreh Chamanian: Anschutz Medical Campus, University of Colorado
Amie L. Meditz: Anschutz Medical Campus, University of Colorado
Tessa Arends: Anschutz Medical Campus, University of Colorado
Martin D. McCarter: School of Medicine, Anschutz Medical Campus, University of Colorado
David N. Levy: New York University College of Dentistry
Eva G. Rakasz: Wisconsin National Primate Research Center, University of Wisconsin-Madison
Pamela J. Skinner: University of Minnesota
Elizabeth Connick: Anschutz Medical Campus, University of Colorado

Nature Communications, 2015, vol. 6, issue 1, 1-16

Abstract: Abstract Human and simian immunodeficiency viruses (HIV and SIV) exploit follicular lymphoid regions by establishing high levels of viral replication and dysregulating humoral immunity. Follicular regulatory T cells (TFR) are a recently characterized subset of lymphocytes that influence the germinal centre response through interactions with follicular helper T cells (TFH). Here, utilizing both human and rhesus macaque models, we show the impact of HIV and SIV infection on TFR number and function. We find that TFR proportionately and numerically expand during infection through mechanisms involving viral entry and replication, TGF-β signalling, low apoptosis rates and the presence of regulatory dendritic cells. Further, TFR exhibit elevated regulatory phenotypes and impair TFH functions during HIV infection. Thus, TFR contribute to inefficient germinal centre responses and inhibit HIV and SIV clearance.

Date: 2015
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9608

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DOI: 10.1038/ncomms9608

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