title: Activation of CD8 T cells normalizes and correlates with the level of infectious provirus in tonsils during highly active antiretroviral therapy in early HIV-1 infection.
abstract: OBJECTIVE
  To study the effects of antiretroviral therapy on T cell activation in blood and tonsils from HIV-1 infected individuals in relation to CD4 cell count, plasma viremia, and infectious HIV-1 provirus.
  
  
  METHODS
  A 48-week study of viral load and T cell subsets in blood and tonsils from 12 HIV-1-positive individuals with a mean CD4 cell number of 400 x 10(6) cells/l treated with a combination of zidovudine, lamivudine, and indinavir.
  
  
  METHODS
  Tonsil biopsies and blood samples were collected at regular intervals. Lymphocytes were phenotyped and quantified by three-color flow cytometry; infectious provirus was quantified by a limiting dilution assay. HIV-1-negative individuals were included as controls.
  
  
  RESULTS
  The fraction of tonsillar CD8 T cells expressing CD69, CD38, or HLA-DR in the patients with suppressed virus replication declined to levels comparable with that in controls by 48 weeks and showed a strong positive correlation with tonsillar infectious provirus and plasma viremia. The level of CD4 T cell activation was within normal range in tonsils throughout the study. The fraction of HLA-DR+ cells within CD4 and CD8 T cells in blood declined rapidly in parallel with plasma viremia but remained slightly higher compared with that in uninfected individuals.
  
  
  CONCLUSIONS
  Antiretroviral therapy normalizes tonsillar CD8 T cell activation in HIV-1-positive individuals in parallel with suppression of viral replication, indicating reduced CD8 cell turnover. Normal tonsillar CD4 T cell activation suggests limited CD4 cell turnover in early HIV infection. Activated CD8 T cells in lymphoid tissue is superior to that in blood as an immunological marker for the virological response to antiretroviral therapy.
authors.affiliation: Department of Microbiology and Immunology, Centre for Research in Virology, University of Bergen, Norway.
authors.forename: A M
authors.initials: AM
authors.lastname: Dyrhol-Riise
authors.forename: P
authors.initials: P
authors.lastname: Voltersvik
authors.forename: J
authors.initials: J
authors.lastname: Olofsson
authors.forename: B
authors.initials: B
authors.lastname: Asjö
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification* / Q000502:physiology; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D019469:Indinavir / Q000008:administration & dosage; D019259:Lamivudine / Q000008:administration & dosage; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins; D009244:NAD+ Nucleosidase / Q000378:metabolism; D014066:Palatine Tonsil / Q000821:virology*; D011533:Proviruses / Q000302:isolation & purification*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013997:Time Factors; D014766:Viremia / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000008:administration & dosage
chemical_list: D019380:Anti-HIV Agents; D015703:Antigens, CD; D000943:Antigens, Differentiation; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D019259:Lamivudine; D015215:Zidovudine; D019469:Indinavir; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1