Epitopes described in "Dysfunctional Epstein-Barr virus (EBV)-specific CD8(+) T lymphocytes and increased EBV load in HIV-1 infected individuals progressing to AIDS-related non-Hodgkin lymphoma."

Article Authors:D van Baarle; E Hovenkamp; M F Callan; K C Wolthers; S Kostense; L C Tan; H G Niesters; A D Osterhaus; A J McMichael; M H van Oers; F Miedema
Article Title:Dysfunctional Epstein-Barr virus (EBV)-specific CD8(+) T lymphocytes and increased EBV load in HIV-1 infected individuals progressing to AIDS-related non-Hodgkin lymphoma.
Reference Detail
Reference ID:1004288
Abstract:Acquired immunodeficiency syndrome-related non-Hodgkin lymphomas (AIDS-NHL) are thought to arise because of loss of Epstein-Barr Virus (EBV)-specific cellular immunity. Here, an investigation was done to determine whether cellular immunity to EBV is lost because of physical loss or dysfunction of EBV-specific cytotoxic T cells. Data on EBV-specific cellular immunity were correlated with EBV load. For comparison, individuals who progressed to AIDS with opportunistic infections (AIDS-OI) and long-term asymptomatics (LTAs) were studied. The number of virus-specific T cells was detected using tetrameric HLA-EBV-peptide complexes; function of these EBV-specific T cells was determined using the interferon-gamma (IFN-gamma) Elispot assay. It was observed that EBV-specific CD8(+) T cells were present in normal numbers in human immunodeficiency virus (HIV)-infected individuals. However, their functional capacity was decreased compared with HIV(-) individuals. In AIDS-NHL patients, EBV-specific T cells were not physically lost in the course of HIV-1 infection but showed progressive loss of their capability to produce IFN-gamma in response to EBV peptides. This loss of function correlated with lower CD4(+) T-cell numbers and was accompanied by increasing EBV load. In HIV-1-infected LTA individuals, in whom CD4(+) T-cell numbers were maintained, and progressors to AIDS-OI, IFN-gamma-producing EBV-specific T cells were stable and EBV load remained stable or decreased in the course of HIV infection, suggestive of immune control. Our data indicate that functional loss of EBV-specific CD8(+) T cells with a concomitant increase in EBV load may play a role in the pathogenesis of AIDS-NHL.
Affiliations:Department of Hematology, University of Amsterdam, Amsterdam, The Netherlands. d_van_baarle@clb.nl
Reference Type:Literature
PubMed ID:11418474
Journal Volume:98
Article Pages:146-55
Journal ISSN:0006-4971
Article Chemical List:Antigens, Viral;DNA, Viral
Article MeSH List:AIDS-Related Opportunistic Infections; Adult; Antigens, Viral(blood; immunology ); CD8-Positive T-Lymphocytes(immunology; pathology; virology ); DNA, Viral(blood ); HIV Infections(blood; immunology; virology ); HIV Long-Term Survivors; HIV-1; Herpesvirus 4, Human(immunology; pathogenicity ); Humans; Lymphoma, AIDS-Related(blood; etiology; virology ); Male; Middle Aged; Time Factors; Viral Load
Curation Last Updated:2016-01-06 18:19:53