title: Interleukin-2 production by polyfunctional HIV-1-specific CD8 T cells is associated with enhanced viral suppression.
abstract: BACKGROUND
  Assays to measure the induction of HIV-1-specific CD8 T-cell responses often rely on measurements of indirect effector function such as chemokine and cytokine production, which may not reflect direct elimination of an invading pathogen. Assessment of the functional ability of CD8 T cells to suppress HIV-1 replication has been viewed as a surrogate marker of an effectual immune response. To further investigate this, we measured the capacity of virus-specific CD8 T cells to inhibit HIV-1 replication in an in vitro suppression assay.
  
  
  METHODS
  We expanded 15 epitope-specific CD8 T-cell lines from peripheral blood mononuclear cells of chronically HIV--infected progressors (n = 5) and controllers (n = 4) who were not on antiretroviral therapy. Cell lines were tested for their ability to produce effector molecules (CD107a, IL-2, IFN-γ, TNF-α, perforin) and suppress virus replication in autologous CD4 T cells.
  
  
  RESULTS
  CD8 T-cell lines from both progressors and controllers had largely similar effector function profiles as determined by intracellular cytokine staining. In contrast, we observed that CD8 T-cell lines derived from controllers show enhanced virus suppression when compared with progressors. Virus suppression was mediated in an major histocompatibility complex-dependent manner and found to correlate with a polyfunctional IL-2 CD8 T-cell response.
  
  
  CONCLUSIONS
  Using a sensitive in vitro suppression assay, we demonstrate that CD8 T-cell-mediated suppression of HIV-1 replication is a marker of HIV-1 control. Suppressive capacity was found to correlate with polyfunctional IL-2 production. Assessment of CD8 T-cell-mediated suppression may be an important tool to evaluate vaccine-induced responses.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Olusimidele T
authors.initials: OT
authors.lastname: Akinsiku
authors.forename: Anju
authors.initials: A
authors.lastname: Bansal
authors.forename: Steffanie
authors.initials: S
authors.lastname: Sabbaj
authors.forename: Sonya L
authors.initials: SL
authors.lastname: Heath
authors.forename: Paul A
authors.initials: PA
authors.lastname: Goepfert
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D018450:Disease Progression; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism*; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D054353:Perforin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019562:Viral Load / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
chemical_list: D007376:Interleukin-2; D052118:Lysosomal-Associated Membrane Protein 1; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; D007371:Interferon-gamma