Functional restoration of human immunodeficiency virus and Epstein-Barr virus-specific CD8(+) T cells during highly active antiretroviral therapy is associated with an increase in CD4(+) T cells

Eur J Immunol. 2002 Apr;32(4):1080-9. doi: 10.1002/1521-4141(200204)32:4<1080::AID-IMMU1080>3.0.CO;2-R.


To investigate the effect of highly active antiretroviral therapy (HAART) on HIV- and Epstein-Barr virus (EBV)-specific CD8(+) T cells, total number and function of these cells was determined in 16 HIV-infected individuals using tetrameric HLA-peptide complexes and IFN-gamma ELISPOT assays after peptide stimulation, respectively. HAART induced a significant decrease in HIV-specific tetramer(+) T cells, whereas EBV-specific tetramer(+) T cells did not change. In addition, individuals who temporarily failed on therapy showed a temporary increase in the number of HIV-specific T cells, suggesting that differences in the pool size of antigen-specific T cells was determined by the presence of antigen. Interestingly, there was an increase in the ratio of IFN-gamma-producing T cells per total number of both HIV- and EBV-specific T cells in the majority of individuals, suggesting that the function of virus-specific T cells is improved in individuals successfully treated with HAART. Despite this relative functional improvement of EBV-specific T cells, no significant changes were observed in EBV load. In four subjects who temporarily failed on HAART, the percentage of IFN-gamma-producing T cells, both for HIV and EBV, paralleled CD4(+) T cell kinetics, suggesting that function seems to be related to differences in CD4(+) T cell numbers. Overall, these data indicate that HAART improves the antigen responsiveness of both HIV- and EBV-specific T cells, which is associated with an increase in CD4(+) T cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cohort Studies
  • HIV Antigens / immunology
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Protease Inhibitors / administration & dosage
  • HIV Protease Inhibitors / therapeutic use
  • HIV-1 / immunology*
  • HLA-A2 Antigen / immunology
  • HLA-B8 Antigen / immunology
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Immunity, Cellular
  • Interferon-gamma / biosynthesis
  • Lymphocyte Activation
  • Lymphocyte Count
  • Macromolecular Substances
  • Male
  • Peptide Fragments / immunology
  • Receptors, Antigen, T-Cell / immunology
  • Reverse Transcriptase Inhibitors / administration & dosage
  • Reverse Transcriptase Inhibitors / therapeutic use
  • T-Lymphocyte Subsets / immunology*
  • Viral Load


  • Anti-HIV Agents
  • HIV Antigens
  • HIV Protease Inhibitors
  • HLA-A2 Antigen
  • HLA-B8 Antigen
  • Macromolecular Substances
  • Peptide Fragments
  • Receptors, Antigen, T-Cell
  • Reverse Transcriptase Inhibitors
  • Interferon-gamma