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Skip Navigation LinksHome > June 19, 2013 - Volume 27 - Issue 10 > The γδ T-cell receptor repertoire is reconstituted in HIV pa...
AIDS:
doi: 10.1097/QAD.0b013e3283611888
Basic Science: Concise Communication

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

Chaudhry, Suchitaa; Cairo, Cristianaa; Venturi, Vanessab; Pauza, C. Davida

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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.

Design: 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.

Conclusion: 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.

© 2013 Lippincott Williams & Wilkins, Inc.

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