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

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...

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Veröffentlicht in:AIDS (London) 2012-07, Vol.26 (12), p.F31-F37
Hauptverfasser: VOLLBRECHT, Thomas, STIRNER, Renate, TUFMAN, Amanda, ROIDER, Julia, HUBER, Rudolf M, BOGNER, Johannes R, LECHNER, Andreas, BOURQUIN, Carole, DRAENERT, Rika
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container_end_page F37
container_issue 12
container_start_page F31
container_title AIDS (London)
container_volume 26
creator VOLLBRECHT, Thomas
STIRNER, Renate
TUFMAN, Amanda
ROIDER, Julia
HUBER, Rudolf M
BOGNER, Johannes R
LECHNER, Andreas
BOURQUIN, Carole
DRAENERT, Rika
description 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.
doi_str_mv 10.1097/QAD.0b013e328354b43f
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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
title Chronic progressive HIV-1 infection is associated with elevated levels of myeloid-derived suppressor cells
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