The ?? T-cell receptor repertoire is reconstituted in HIV patients after prolonged antiretroviral therapy.
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ABSTRACT: Determine whether reconstitution of V?2V?2 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.Perform a cross-sectional analysis of the T-cell receptor complexity of V?2 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 V?2 repertoire loss or reconstitution.T-cell receptor V?2 chain DNA clones (up to 300 per patient sample) were sequenced and aligned to enumerate the antigen-reactive subset with V?2-J?1.2 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.Patients with prolonged virus suppression due to antiretroviral therapy reconstituted the V?2 T-cell repertoire to near-normal levels. Natural virus suppressors were similar to the treatment group. Severe defects in the V?2 T-cell receptor repertoire were observed in patients with chronic viremia despite the absence of overt disease.Prolonged HIV suppression with antiretroviral therapy leads to reconstitution of the V?2V?2 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.
SUBMITTER: Chaudhry S
PROVIDER: S-EPMC4217204 | biostudies-literature | 2013 Jun
REPOSITORIES: biostudies-literature
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