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
van Baarle D., Hovenkamp E., Callan MFC., Wolthers KC., Kostense S., Tan LC., Niesters HGM., Osterhaus ADME., McMichael AJ., van Oers MHJ., Miedema F.
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-γ (IFN-γ) 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-γ 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-γ–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.