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 CD11b+ CD14− CD33+ CD15+ MDSC levels than healthy controls (P= 0.01). MDSC frequencies showed a positive correlation with viral load (r 2= 0.24, P= 0.0002) and a negative correlation with CD4 cell count (r 2= 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, CD11b+ CD14− CD33+ CD15+ MDSC induced the expansion of CD4+ CD25+ FoxP3+ 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.