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, Elizabeth Connick

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number8608
JournalNature communications
Volume6
DOIs
StatePublished - Oct 20 2015

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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