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
January 2001
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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.
- Male
- Comparative Study
- Adult
- Humans
- Research Support, Non-U.S. Gov't
- Middle Aged
- Time Factors
- HIV-1
- Viral Load
- DNA, Viral/blood
- AIDS-Related Opportunistic Infections
- Antigens, Viral/blood/immunology
- CD8-Positive T-Lymphocytes/*immunology/*pathology/virology
- HIV Infections/blood/*immunology/virology
- HIV Long-Term Survivors
- Herpesvirus 4, Human/*immunology/pathogenicity
- Lymphoma, AIDS-Related/blood/etiology/*virology
- number
- t cells
- ebv-specific
- ebv load
- tetramer
- figure
- infection
- patient
- t-cell
- tetramer t cells
- individual
- aids-nhl
- elispot assay
- virus
- ebv-specific t cells
- aids-nhl patients
- assay
- staining
- response
- percentage