Follicular regulatory T cells are highly permissive to R5-tropic HIV-1

Shannon M. Miller, Brodie Miles, Kejun Guo, Joy Folkvord, Amie L. Meditz, Martin D. McCarter, David Levy, Samantha MaWhinney, Mario L. Santiago, Elizabeth Connick

Research output: Contribution to journalArticle

Abstract

Follicular regulatory T (TFR) cells are a subset of CD4+ T cells in secondary lymphoid follicles. TFR cells were previously included in the follicular helper T (TFH) cell subset, which consists of cells that are highly permissive to HIV-1. The permissivity of TFR cells to HIV-1 is unknown. We find that TFR cells are more permissive than TFH cells to R5-tropic HIV-1 ex vivo. TFR cells expressed more CCR5 and CD4 and supported higher frequencies of viral fusion. Differences in Ki67 expression correlated with HIV-1 replication. Inhibiting cellular proliferation reduced Ki67 expression and HIV-1 replication. Lymph node cells from untreated HIV-infected individuals revealed that TFR cells harbored the highest concentrations of HIV-1 RNA and highest levels of Ki67 expression. These data demonstrate that TFR cells are highly permissive to R5-tropic HIV-1 both ex vivo and in vivo. This is likely related to elevated CCR5 levels combined with a heightened proliferative state and suggests that TFR cells contribute to persistent R5-tropic HIV-1 replication in vivo.

Original languageEnglish (US)
Article numbere00430-17
JournalJournal of Virology
Volume91
Issue number17
DOIs
StatePublished - Sep 1 2017

Fingerprint

Regulatory T-Lymphocytes
Human immunodeficiency virus 1
HIV-1
tropics
T-lymphocytes
cells
T-Lymphocyte Subsets
Helper-Inducer T-Lymphocytes
lymph nodes
cell proliferation
Lymph Nodes
Cell Proliferation
HIV
RNA

Keywords

  • Follicular helper T cell
  • Follicular regulatory T cell
  • HIV pathogenesis
  • HIV replication
  • Secondary lymphoid follicle

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Miller, S. M., Miles, B., Guo, K., Folkvord, J., Meditz, A. L., McCarter, M. D., ... Connick, E. (2017). Follicular regulatory T cells are highly permissive to R5-tropic HIV-1. Journal of Virology, 91(17), [e00430-17]. https://doi.org/10.1128/JVI.00430-17

Follicular regulatory T cells are highly permissive to R5-tropic HIV-1. / Miller, Shannon M.; Miles, Brodie; Guo, Kejun; Folkvord, Joy; Meditz, Amie L.; McCarter, Martin D.; Levy, David; MaWhinney, Samantha; Santiago, Mario L.; Connick, Elizabeth.

In: Journal of Virology, Vol. 91, No. 17, e00430-17, 01.09.2017.

Research output: Contribution to journalArticle

Miller, SM, Miles, B, Guo, K, Folkvord, J, Meditz, AL, McCarter, MD, Levy, D, MaWhinney, S, Santiago, ML & Connick, E 2017, 'Follicular regulatory T cells are highly permissive to R5-tropic HIV-1', Journal of Virology, vol. 91, no. 17, e00430-17. https://doi.org/10.1128/JVI.00430-17
Miller SM, Miles B, Guo K, Folkvord J, Meditz AL, McCarter MD et al. Follicular regulatory T cells are highly permissive to R5-tropic HIV-1. Journal of Virology. 2017 Sep 1;91(17). e00430-17. https://doi.org/10.1128/JVI.00430-17
Miller, Shannon M. ; Miles, Brodie ; Guo, Kejun ; Folkvord, Joy ; Meditz, Amie L. ; McCarter, Martin D. ; Levy, David ; MaWhinney, Samantha ; Santiago, Mario L. ; Connick, Elizabeth. / Follicular regulatory T cells are highly permissive to R5-tropic HIV-1. In: Journal of Virology. 2017 ; Vol. 91, No. 17.
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