title: 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.
abstract: 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.
authors.affiliation: Department of Clinical Viro-Immunology, CLB and Laboratory for Experimental and Clinical Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. s.kostense@crucell.com
authors.forename: Stefan
authors.initials: S
authors.lastname: Kostense
authors.forename: Sigrid A
authors.initials: SA
authors.lastname: Otto
authors.forename: Gerlinde J
authors.initials: GJ
authors.lastname: Knol
authors.forename: Erik H
authors.initials: EH
authors.lastname: Manting
authors.forename: Nening M
authors.initials: NM
authors.lastname: Nanlohy
authors.forename: Christine
authors.initials: C
authors.lastname: Jansen
authors.forename: Joep M A
authors.initials: JM
authors.lastname: Lange
authors.forename: Marinus H J
authors.initials: MH
authors.lastname: van Oers
authors.forename: Frank
authors.initials: F
authors.lastname: Miedema
authors.forename: Debbie
authors.initials: D
authors.lastname: van Baarle
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D015497:HIV-1 / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D015795:HLA-B8 Antigen / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D046911:Macromolecular Substances; D008297:Male; D010446:Peptide Fragments / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D015488:HIV Antigens; D017320:HIV Protease Inhibitors; D015789:HLA-A2 Antigen; D015795:HLA-B8 Antigen; D046911:Macromolecular Substances; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D018894:Reverse Transcriptase Inhibitors; D007371:Interferon-gamma