Impact of Persistent HIV Replication on CD4 Negative Vγ2Vδ2 T Cells

Background. CD4- V gamma 2V delta 2 T cells are depleted during human immunodeficiency virus (HIV) infection but can recover to near normal levels in patients who spontaneously control viremia in the absence of therapy. By contrasting V gamma 2V delta 2 T-cell numbers, phenotype, and T-cell receptor (TCR) repertoire, we investigate the dynamic tension between active immunity and progressive T-cell destruction during persistent viremia. Methods. Peripheral blood V gamma 2V delta 2 T-cell levels and phenotypes were characterized by flow cytometry. Lymphoproliferation assays measured functional responses. Spectratyping characterized damage to the TCR repertoire. Results. Levels, responses to antigen and the proportion of T effector memory V gamma 2V delta 2 T cells in patients with persistent viremia, were intermediate between patients with natural virus suppression (NVS) and patients receiving antiretroviral therapy. Damage to the TCR gamma-2 chain repertoire and depletion of CD56+ V gamma 2V delta 2 T cells were more pronounced in viremic patients, compared with antiretroviral therapy recipients and patients with natural virus suppression. Conclusions. Characteristics of V gamma 2V delta 2 T cells in viremic patients reflect both active responses (increasing cell numbers, better antigen responses, and higher proportion of effector memory cells) and ongoing damage (repertoire changes and loss of CD561 cells). Unlike patients who control viremia to undetectable levels, V gamma 2V delta 2 T cells are diminished during persistent viremia and may eventually be lost because of progressive destruction of the TCR repertoire.