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

Follicular Regulatory T Cells Are Highly Permissive to R5-Tropic HIV-1.
Author Information (click to view)

Miller SM, Miles B, Guo K, Folkvord J, Meditz AL, McCarter MD, Levy DN, MaWhinney S, Santiago ML, Connick E,


Miller SM, Miles B, Guo K, Folkvord J, Meditz AL, McCarter MD, Levy DN, MaWhinney S, Santiago ML, Connick E, (click to view)

Miller SM, Miles B, Guo K, Folkvord J, Meditz AL, McCarter MD, Levy DN, MaWhinney S, Santiago ML, Connick E,

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Journal of virology 2017 08 1091(17) pii 10.1128/JVI.00430-17

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.

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