title: HIV-Specific CD8+ T Cell-Mediated Viral Suppression Correlates With the Expression of CD57.
abstract: BACKGROUND
  Virus-specific CD8(+) T-cell responses are believed to play an important role in the control of HIV-1 infection; however, what constitutes an effective HIV-1 CD8(+) T-cell response remains a topic of debate. The ex vivo viral suppressive capacity was measured of CD8(+) T cells from 44 HIV-1-positive individuals. The phenotypic and cytokine profiles, and also the specificity of the CD8(+) T cells, were correlated with the suppression of HIV-1 replication. We also aimed to determine whether antiretroviral therapy (ART) had any positive effect on the HIV-1 suppressive CD8(+) T cells.
  
  
  METHODS
  Ex vivo suppression assay was used to evaluate the ability of CD8(+) T cells to suppress HIV-1 replication in autologous CD4(+) T cells. The CD107a, interferon-γ, interleukin-2, tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein-1β (MIP-1β) responses to HIV-1 were evaluated by intracellular staining. The phenotypic profile of CD8(+) T cells was determined by whole blood staining.
  
  
  RESULTS
  The expression of CD57 on effector CD8(+) T cells correlated with the suppression of HIV-1 replication and to the duration of ART. CD107a and tumor necrosis factor-α expression levels were significantly higher in individuals with ex vivo suppressive activity compared with individuals without suppressive activity.
  
  
  CONCLUSIONS
  Standard in vitro assays measuring one or several cytokines do not correlate with the functional viral suppressive capacity of CD8(+) T cells from HIV-1-positive individuals. The best correlation of viral suppression was found to be CD57 expression. CD57 expression correlated with the duration of ART, suggesting that ART restores the cytotoxic capacity of CD8(+) T lymphocytes.
authors.affiliation: *Virus Research and Development Laboratory, Department of Microbial Diagnostic and Virology, Statens Serum Institut, Copenhagen, Denmark;†Department of Infectious Diseases, Odense University Hospital, Odense, Denmark;‡Infectious Disease Research Unit, Clinical Institute, University of Southern Denmark, Odense, Denmark;§Viro-immunology Research Unit, Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark; and‖Department of Infectious Diseases, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
authors.forename: Sanne S
authors.initials: SS
authors.lastname: Jensen
authors.forename: Jeanette Linnea
authors.initials: JL
authors.lastname: Tingstedt
authors.forename: Tine Kochendorf
authors.initials: TK
authors.lastname: Larsen
authors.forename: Lea
authors.initials: L
authors.lastname: Brandt
authors.forename: Jan
authors.initials: J
authors.lastname: Gerstoft
authors.forename: Gitte
authors.initials: G
authors.lastname: Kronborg
authors.forename: Court
authors.initials: C
authors.lastname: Pedersen
authors.forename: Anders
authors.initials: A
authors.lastname: Fomsgaard
authors.forename: Ingrid
authors.initials: I
authors.lastname: Karlsson
mesh_terms: D044966:Anti-Retroviral Agents / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D018959:CD57 Antigens / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D054407:Chemokine CCL4 / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019562:Viral Load / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
chemical_list: D044966:Anti-Retroviral Agents; C066507:CCL4 protein, human; D018959:CD57 Antigens; D054407:Chemokine CCL4; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma