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AIDS. 2012 Jul 31;26(12):F31-7. doi: 10.1097/QAD.0b013e328354b43f.

Chronic progressive HIV-1 infection is associated with elevated levels of myeloid-derived suppressor cells.

Author information

1
Medizinische Klinik und Poliklinik IV, Munich, Germany.

Abstract

OBJECTIVES:

Myeloid-derived suppressor cells (MDSCs) have been described as suppressors of T-cell functions in many tumor models. However, MDSC in HIV-1 infection have not been studied to date. As impaired T-cell function is a hallmark of chronic progressive HIV-1 infection, we hypothesized that MDSC also play a role here.

METHODS:

Surface staining and flow cytometry analysis were performed on freshly isolated peripheral blood mononuclear cells (PBMC) of HIV-infected individuals and compared to healthy controls and individuals with lung carcinoma. MDSC of late-stage HIV-infected individuals were isolated using magnetic beads and cocultured with the respective CD8 T cells for evaluation of proliferative capacity.

RESULTS:

We found that chronically HIV-infected HAART-naive individuals had significantly higher CD11bCD14CD33CD15 MDSC levels than healthy controls (P = 0.01). MDSC frequencies showed a positive correlation with viral load (r = 0.24, P = 0.0002) and a negative correlation with CD4 cell count (r = 0.29, P < 0.0001). Initiation of HAART led to a rapid drop in MDSC levels. MDSC from HIV-infected progressors restricted the proliferative capacity of CD8 T cells from healthy donors and of Gag/Nef-specific CD8 T cells from HIV-controllers in vitro. Furthermore, CD11bCD14CD33CD15 MDSC induced the expansion of CD4CD25FoxP3 regulatory T cells when coincubated with PBMC from controllers in vitro.

CONCLUSION:

We conclude that chronic uncontrolled HIV-infection is associated with elevated levels of MDSC, which potentially contribute to the impaired T-cell responses characteristic for the progressive disease stage.

PMID:
22526518
DOI:
10.1097/QAD.0b013e328354b43f
[Indexed for MEDLINE]

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