Dysfunctional Epstein-Barr virus (EBV)-specific CD8(+) T lymphocytes and increased EBV load in HIV-1 infected individuals progressing to AIDS-relatednon-Hodgkin lymphoma

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 cel lular immunity to EBV is lost because of physical loss or dysfunction of EB V-specific cytotoxic T cells. Data on EBV-specific cellular immunity were c orrelated 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 tetr americ HLA-EBV-peptide complexes; function of these EBV-specific T cells wa s determined using the interferon-gamma (IFN-gamma) Elispot assay. It was o bserved that EBV-specific CD8(+) T cells were present in normal numbers in human immunodeficiency virus (HIV)-infected individuals. However, their fun ctional capacity was decreased compared with HIV- individuals. In AIDS-NHL patients, EBV-specific T cells were not physically lost in the course of HI V-1 infection but showed progressive loss of their capability to produce IF N-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 maintain ed, and progressors to AIDS-OI, IFN-gamma -producing EBV-specific T cells w ere stable and EBV load remained stable or decreased in the course of HIV i nfection, suggestive of immune control. Our data indicate that functional l oss of EBV-specific CD8(+) T cells with a concomitant increase in EBV load may play a role in the pathogenesis of AIDS-NHL. (C) 2001 by The American S ociety of Hematology.