Format

Send to

Choose Destination
J Virol. 2017 Aug 10;91(17). pii: e00430-17. doi: 10.1128/JVI.00430-17. Print 2017 Sep 1.

Follicular Regulatory T Cells Are Highly Permissive to R5-Tropic HIV-1.

Author information

1
Department of Immunology and Microbiology, School of Medicine, Anschutz Medical Campus, University of Colorado Denver, Aurora, Colorado, USA.
2
Division of Infectious Diseases, Department of Medicine, Anschutz Medical Campus, University of Colorado Denver, Aurora, Colorado, USA.
3
Beacon Center for Infectious Diseases, Boulder, Colorado, USA.
4
Department of Surgery, Anschutz Medical Campus, University of Colorado Denver, Aurora, Colorado, USA.
5
Department of Basic Science, New York University College of Dentistry, New York, New York, USA.
6
Department of Biostatistics and Informatics, Anschutz Medical Campus, University of Colorado Denver, Aurora, Colorado, USA.
7
Department of Immunology and Microbiology, School of Medicine, Anschutz Medical Campus, University of Colorado Denver, Aurora, Colorado, USA connicke@email.arizona.edu.

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 vivoIMPORTANCE In chronic, untreated HIV-1 infection, viral replication is concentrated in secondary lymphoid follicles. Within secondary lymphoid follicles, follicular helper T (TFH) cells have previously been shown to be highly permissive to HIV-1. Recently, another subset of T cells in secondary lymphoid follicles was described, follicular regulatory T (TFR) cells. These cells share some phenotypic characteristics with TFH cells, and studies that showed that TFH cells are highly permissive to HIV-1 included TFR cells in their definition of TFH cells. The permissivity of TFR cells to HIV-1 has not previously been described. Here, we show that TFR cells are highly permissive to HIV-1 both ex vivo and in vivo The expression of Ki67, a marker of proliferative capacity, is predictive of expression of viral proteins, and downregulating Ki67 leads to concurrent decreases in expression of viral proteins. Our study provides new insight into HIV-1 replication and a potential new cell type to target for future treatment.

KEYWORDS:

HIV pathogenesis; HIV replication; follicular helper T cell; follicular regulatory T cell; secondary lymphoid follicle

PMID:
28615202
PMCID:
PMC5553166
DOI:
10.1128/JVI.00430-17
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for PubMed Central Icon for University of Colorado, Strauss Health Sciences Library
Loading ...
Support Center