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

Author

Listed:
  • 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
    Present address: Beacon Clinic, Boulder Community Hospital, Boulder, Colorado 80301, USA.)

  • 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)

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.

Suggested Citation

  • 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 & El, 2015. "Follicular regulatory T cells impair follicular T helper cells in HIV and SIV infection," Nature Communications, Nature, vol. 6(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9608
    DOI: 10.1038/ncomms9608
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