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 Levy, Eva G. Rakasz, Pamela J. Skinner, Elizabeth Connick

Research output: Contribution to journalArticle

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

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human immunodeficiency virus
T-cells
infectious diseases
Regulatory T-Lymphocytes
Helper-Inducer T-Lymphocytes
HIV Infections
Germinal Center
HIV
Lymphocytes
cells
Viruses
Simian Immunodeficiency Virus
Lymphocyte Subsets
Apoptosis
Humoral Immunity
Macaca mulatta
Dendritic Cells
phenotype
lymphocytes
immunity

ASJC Scopus subject areas

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

Cite this

Miles, B., Miller, S. M., Folkvord, J. M., Kimball, A., Chamanian, M., Meditz, A. L., ... Connick, E. (2015). Follicular regulatory T cells impair follicular T helper cells in HIV and SIV infection. Nature Communications, 6, [8608]. https://doi.org/10.1038/ncomms9608

Follicular regulatory T cells impair follicular T helper cells in HIV and SIV infection. / Miles, Brodie; Miller, Shannon M.; Folkvord, Joy M.; Kimball, Abigail; Chamanian, Mastooreh; Meditz, Amie L.; Arends, Tessa; McCarter, Martin D.; Levy, David; Rakasz, Eva G.; Skinner, Pamela J.; Connick, Elizabeth.

In: Nature Communications, Vol. 6, 8608, 20.10.2015.

Research output: Contribution to journalArticle

Miles, B, Miller, SM, Folkvord, JM, Kimball, A, Chamanian, M, Meditz, AL, Arends, T, McCarter, MD, Levy, D, Rakasz, EG, Skinner, PJ & Connick, E 2015, 'Follicular regulatory T cells impair follicular T helper cells in HIV and SIV infection', Nature Communications, vol. 6, 8608. https://doi.org/10.1038/ncomms9608
Miles B, Miller SM, Folkvord JM, Kimball A, Chamanian M, Meditz AL et al. Follicular regulatory T cells impair follicular T helper cells in HIV and SIV infection. Nature Communications. 2015 Oct 20;6. 8608. https://doi.org/10.1038/ncomms9608
Miles, Brodie ; Miller, Shannon M. ; Folkvord, Joy M. ; Kimball, Abigail ; Chamanian, Mastooreh ; Meditz, Amie L. ; Arends, Tessa ; McCarter, Martin D. ; Levy, David ; Rakasz, Eva G. ; Skinner, Pamela J. ; Connick, Elizabeth. / Follicular regulatory T cells impair follicular T helper cells in HIV and SIV infection. In: Nature Communications. 2015 ; Vol. 6.
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