Faculté des sciences

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

Vollbrecht, Thomas ; Stirner, Renate ; Tufman, Amanda ; Roider, Julia ; Huber, Rudolf M. ; Bogner, Johannes R. ; Lechner, Andreas ; Bourquin, Carole ; Draenert, Rika

In: AIDS, 2012, vol. 26, no. 12, p. F31–F37

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... Plus

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    Summary
    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 (r² = 0.24, P = 0.0002) and a negative correlation with CD4 cell count (r² = 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.