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

doi:10.1097/QAD.0b013e328354b43f

Back

Journal article

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

Vollbrecht, Thomas Medizinische Klinik und Poliklinik IV, Klinikum der LMU, Munich, Germany
Stirner, Renate Medizinische Klinik und Poliklinik IV, Klinikum der LMU, Munich, Germany
Tufman, Amanda Medizinische Klinik und Poliklinik V, Klinikum der LMU, Munich, Germany
Roider, Julia Medizinische Klinik und Poliklinik IV, Klinikum der LMU, Munich, Germany
Huber, Rudolf M. Medizinische Klinik und Poliklinik V, Klinikum der LMU, Munich, Germany
Bogner, Johannes R. Medizinische Klinik und Poliklinik IV, Klinikum der LMU, Munich, Germany
Lechner, Andreas Medizinische Klinik und Poliklinik IV, Klinikum der LMU, Munich, Germany
Bourquin, Carole Medizinische Klinik und Poliklinik IV, Klinikum der LMU, Munich, Germany - Department of Medicine, University of Fribourg, Fribourg, Switzerland.
Draenert, Rika Medizinische Klinik und Poliklinik IV, Klinikum der LMU, Munich, Germany

31.07.2012

Published in:

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

myeloid-derived suppressor cell

English 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.

Faculty

Faculté des sciences et de médecine

Department

Département de Médecine

Language