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J Infect Dis. 2014 Feb 1;209(3):441-51. doi: 10.1093/infdis/jit469. Epub 2013 Sep 1.

HIV type 1 gp120-induced expansion of myeloid derived suppressor cells is dependent on interleukin 6 and suppresses immunity.

Author information

1
Department of Pediatrics, Division of Infectious Diseases, University of California, San Diego, La Jolla.

Abstract

BACKGROUND:

Factors responsible for myeloid-derived suppressor cell (MDSC) expansion and T-cell dysfunction during human immunodeficiency virus type 1 (HIV) infection are unknown. This study investigated the role of MDSCs during HIV infection.

METHODS:

Peripheral blood mononuclear cells (PBMCs) were cultured with gp120 and infectious or inactivated HIV, with or without anti-interleukin 6 (IL-6) antibody. CD33(+), CD4(+), and CD8(+) cells were isolated from PBMCs and cocultured in the presence or absence of inducible nitric oxide synthase (iNOS), reactive oxygen species (ROS), and arginase 1 inhibitors. CD11b(+)CD33(+)CD14(+)HLA-DR(-/lo) MDSCs, phosphorylated STAT3 (pSTAT3), and CD4(+)CD25(+)FoxP3(+) cells were evaluated by flow cytometry. IL-6, interferon γ (IFN-γ), interleukin 10 (IL-10), and gp120 levels were quantified by an enzyme-linked immunosorbent assay.

RESULTS:

MDSCs expanded when PBMCs were exposed to infectious or inactivated HIV. Exposure to gp120 led to MDSC expansion, with increases in IL-6 levels and pSTAT3 expression. Anti-IL-6 abrogated MDSC expansion and pSTAT3 expression. gp120-expanded CD33(+) MDSCs inhibited IFN-γ release from autologous T cells, which was restored upon ROS and iNOS inhibition. gp120-expanded CD33(+) MDSCs increased IL-10 and CD4(+)CD25(+)FoxP3(+) regulatory T-cell levels in CD4(+) T-cell cocultures. Finally, high frequencies of MDSCs were present in HIV-infected persons, compared with healthy controls.

CONCLUSIONS:

These findings demonstrate that HIV gp120 induces IL-6 and MDSC expansion, which contributes to immune suppression by modulating cytokine and cellular responses.

KEYWORDS:

HIV-1; IL-6; Myeloid Derived Suppressor Cells; gp120

PMID:
23999600
PMCID:
PMC3883171
DOI:
10.1093/infdis/jit469
[Indexed for MEDLINE]
Free PMC Article

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