Volume 9 Supplement 2
Chronic progressive HIV-1 infection is associated with elevated levels of myeloid-derived suppressor cells
© Vollbrecht et al; licensee BioMed Central Ltd. 2012
Published: 13 September 2012
Myeloid-derived suppressor cells (MDSC) 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.
Surface staining and FACS analysis were performed on freshly isolated PBMC of HIV-infected individuals and compared to healthy controls and individuals with lung carcinoma. MDSC of late-stage HIV-infected subjects were isolated using magnetic beads and co-cultured with the respective CD8 T cells for evaluation of proliferative capacity.
We found that chronically HIV-infected HAART-naïve 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 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 co-incubated with PBMC from controllers in vitro.
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.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.