The γδ T-cell receptor repertoire is reconstituted in HIV patients after prolonged antiretroviral therapy

Objective:Determine whether reconstitution of V2V2 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.Design:Perform a cross-sectional analysis of the T-cell receptor complexity of V2 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 V2 repertoire loss or reconstitution.Methods:T-cell receptor V2 chain DNA clones (up to 300 per patient sample) were sequenced and aligned to enumerate the antigen-reactive subset with V2-J1.2 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 V2 T-cell repertoire to near-normal levels. Natural virus suppressors were similar to the treatment group. Severe defects in the V2 T-cell receptor repertoire were observed in patients with chronic viremia despite the absence of overt disease.Conclusion:Prolonged HIV suppression with antiretroviral therapy leads to reconstitution of the V2V2 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.