title: Chronic progressive HIV-1 infection is associated with elevated levels of myeloid-derived suppressor cells.
abstract: OBJECTIVE
  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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Medizinische Klinik und Poliklinik IV, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vollbrecht
authors.forename: Renate
authors.initials: R
authors.lastname: Stirner
authors.forename: Amanda
authors.initials: A
authors.lastname: Tufman
authors.forename: Julia
authors.initials: J
authors.lastname: Roider
authors.forename: Rudolf M
authors.initials: RM
authors.lastname: Huber
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Bogner
authors.forename: Andreas
authors.initials: A
authors.lastname: Lechner
authors.forename: Carole
authors.initials: C
authors.lastname: Bourquin
authors.forename: Rika
authors.initials: R
authors.lastname: Draenert
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology; D016022:Case-Control Studies; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology; D022423:Myeloid Cells / Q000187:drug effects / Q000276:immunology*; D019562:Viral Load