title: The γδ T-cell receptor repertoire is reconstituted in HIV patients after prolonged antiretroviral therapy.
abstract: OBJECTIVE
  Determine whether reconstitution of Vγ2Vδ2 T cells in patients with HIV is due to new cell synthesis with recovery of the T-cell receptor repertoire or proliferative expansion of residual cells from the time of treatment initiation.
  
  
  METHODS
  Perform a cross-sectional analysis of the T-cell receptor complexity of Vγ2 chain in patients treated for HIV, natural virus suppressors who control viremia to undetectable levels, patients with chronic low-level viremia in the absence of therapy, and uninfected controls. Apply quantitative methods for repertoire analysis to assess the degree of Vδ2 repertoire loss or reconstitution.
  
  
  METHODS
  T-cell receptor Vγ2 chain DNA clones (up to 300 per patient sample) were sequenced and aligned to enumerate the antigen-reactive subset with Vγ2-Jγ1.2 rearrangements. Predominant shared (public) sequences in each patient were compared to a reference library of public sequences from uninfected controls to assess the extent of similarity. Repertoire comparisons were quantified through bioinformatics testing.
  
  
  RESULTS
  Patients with prolonged virus suppression due to antiretroviral therapy reconstituted the Vγ2 T-cell repertoire to near-normal levels. Natural virus suppressors were similar to the treatment group. Severe defects in the Vγ2 T-cell receptor repertoire were observed in patients with chronic viremia despite the absence of overt disease.
  
  
  CONCLUSIONS
  Prolonged HIV suppression with antiretroviral therapy leads to reconstitution of the Vγ2Vδ2 T-cell subset deleted in HIV disease. Direct evidence for repair of the T-cell receptor repertoire supports a view that treatment-associated immune reconstitution is due to new cell synthesis and not to expansion of residual cell populations.
authors.affiliation: Division of Basic Science and Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 20201, USA.
authors.forename: Suchita
authors.initials: S
authors.lastname: Chaudhry
authors.forename: Cristiana
authors.initials: C
authors.lastname: Cairo
authors.forename: Vanessa
authors.initials: V
authors.lastname: Venturi
authors.forename: C David
authors.initials: CD
authors.lastname: Pauza
mesh_terms: D044966:Anti-Retroviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000187:drug effects / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D044966:Anti-Retroviral Agents; D016692:Receptors, Antigen, T-Cell, gamma-delta