title: Lack of Epstein-Barr virus- and HIV-specific CD27- CD8+ T cells is associated with progression to viral disease in HIV-infection.
abstract: OBJECTIVE
  Despite readily detectable virus-specific CD8+ T cells in most HIV-infected patients, immune surveillance is eventually lost, leading to progression to AIDS. To investigate the underlying mechanism of this loss of immune control phenotypic analysis of HIV- and Epstein-Barr virus (EBV)-specific CD8+ T cells was performed.
  
  
  METHODS
  In three clinically distinct groups, long-term asymptomatics, progressors to opportunistic infections and progressors to EBV-associated non-Hodgkin lymphoma's (NHL), both number and phenotype of virus-specific CD8+ T cells was studied longitudinally.
  
  
  METHODS
  The number of HIV- and EBV-specific T cells were determined using HLA-peptide tetrameric complexes. The phenotype of these virus-specific T cells was investigated by costaining with CD27 and CD45RO and thereby identifying specific subsets of CD8+ T cells.
  
  
  RESULTS
  Individuals co-infected with HIV and EBV persistently had low numbers of HIV-specific CD27- T cells, in contrast to rising numbers of EBV-specific CD27- CD8+ T cells. However, HIV-infected individuals developing EBV-associated AIDS-related NHL had very low numbers of EBV-specific CD27- CD8+ T cells. Higher numbers of HIV-specific CD27- CD8+ T cells were associated with delayed disease progression. Virus-specific CD27- T cells, compared with CD27+ T cells showed elevated interferon-gamma production in response to viral peptides in vitro, indicative for strong effector function.
  
  
  CONCLUSIONS
  Taken together, our data indicate that virus-specific CD27- T cells may be important effector T cells in controlling chronic viral infections in humans and that lack of differentiation into CD27- effector T cells may lead to progression of viral disease.
authors.affiliation: Department of Clinical Viro-Immunology, CLB/Sanquin & Landsteiner Laboratory of the Academic Medical Center, University of Amsterdam, The Netherlands. d_van_baarle@clb.nl
authors.forename: Debbie
authors.initials: D
authors.lastname: van Baarle
authors.forename: Stefan
authors.initials: S
authors.lastname: Kostense
authors.forename: Egbert
authors.initials: E
authors.lastname: Hovenkamp
authors.forename: Graham
authors.initials: G
authors.lastname: Ogg
authors.forename: Nening
authors.initials: N
authors.lastname: Nanlohy
authors.forename: Margaret F C
authors.initials: MF
authors.lastname: Callan
authors.forename: Nicole H T M
authors.initials: NH
authors.lastname: Dukers
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: Marinus H J
authors.initials: MH
authors.lastname: van Oers
authors.forename: Frank
authors.initials: F
authors.lastname: Miedema
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D018450:Disease Progression; D015658:HIV Infections / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D016483:Lymphoma, AIDS-Related / Q000276:immunology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*
chemical_list: D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D007371:Interferon-gamma