Vollbrecht, Thomas Stirner, Renate Tufman, Amanda Roider, Julia Huber, Rudolf M. Bogner, Johannes R. Lechner, Andreas Bourquin, Carole Draenert, Rika 2012-07-31 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 (<em>P</em> = 0.01). MDSC frequencies showed a positive correlation with viral load (<em>r</em>² = 0.24, <em>P</em> = 0.0002) and a negative correlation with CD4 cell count (<em>r</em>² = 0.29, <em>P</em> < 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 <em>in vitro</em>. Furthermore, CD11b⁺CD14⁻CD33⁺CD15⁺ MDSC induced the expansion of CD4⁺CD25⁺FoxP3⁺ regulatory T cells when coincubated with PBMC from controllers <em>in vitro</em>.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. application/pdf https://folia.unifr.ch/global/documents/302815 https://folia.unifr.ch/documents/302815/files/bou_cph.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1097/QAD.0b013e328354b43f info:eu-repo/semantics/openAccess License undefined AIDS. - 2012, vol. 26, no. 12, p. F31–F37 cancers CD8 T-cell function cellular immunity myeloid-derived suppressor cell progressive HIV infection info:eu-repo/classification/udc/57 Chronic progressive HIV 1 infection is associated with elevated levels of myeloid derived suppressor cells http://purl.org/coar/resource_type/c_6501