Impact of Persistent HIV Replication on CD4 Negative Vγ2Vδ2 T Cells

BACKGROUND: CD4- Vγ2Vδ2 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 Vγ2Vδ2 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 Vγ2Vδ2 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 Vγ2Vδ2 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 γ-2 chain repertoire and depletion of CD56+ Vγ2Vδ2 T cells were more pronounced in viremic patients, compared with antiretroviral therapy recipients and patients with natural virus suppression. CONCLUSIONS: Characteristics of Vγ2Vδ2 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 CD56+ cells). Unlike patients who control viremia to undetectable levels, Vγ2Vδ2 T cells are diminished during persistent viremia and may eventually be lost because of progressive destruction of the TCR repertoire.