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

• Published in: AIDS (London) Vol. 26; no. 12; pp. F31 - F37
• Main Authors: VOLLBRECHT, Thomas, STIRNER, Renate, TUFMAN, Amanda, ROIDER, Julia, HUBER, Rudolf M, BOGNER, Johannes R, LECHNER, Andreas, BOURQUIN, Carole, DRAENERT, Rika
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 31-07-2012
• Subjects: AIDS/HIV; Antiretroviral Therapy, Highly Active; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - immunology; Case-Control Studies; CD8-Positive T-Lymphocytes - immunology; Flow Cytometry; HIV Infections - drug therapy; HIV Infections - immunology; HIV-1 - immunology; Human immunodeficiency virus 1; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Lung Neoplasms - immunology; Medical sciences; Myeloid Cells - drug effects; Myeloid Cells - immunology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Immunopathology; Cell function; HIV-1 virus; progressive HIV infection; Retroviridae; AIDS; Cellular immunity; Malignant tumor; Immune deficiency; Lentivirus; Myeloid cell; Infection; Virus; Progressive; Chronic; Immunological investigation; Viral disease; myeloid-derived suppressor cell; T-Lymphocyte; cancers; CD8 T-cell function; Human immunodeficiency virus; Cancer
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/QAD.0b013e328354b43f

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.
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.
We found that chronically HIV-infected HAART-naive individuals had significantly higher CD11bCD14CD33CD15 MDSC levels than healthy controls (P = 0.01). MDSC frequencies showed a positive correlation with viral load (r = 0.24, P = 0.0002) and a negative correlation with CD4 cell count (r = 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, CD11bCD14CD33CD15 MDSC induced the expansion of CD4CD25FoxP3 regulatory T cells when coincubated 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.