Nature Communications · 2019 · 215 citations · 41 references
Life SciencesImmunologyPharmacotherapyImmunopharmacologyImmunoregulationImmunotherapyAntiretroviral TherapyCheckpoint Inhibitor TherapyImmune Checkpoint InhibitorsImmune CheckpointsT Cell ActivationViral LatencyCd4 Positive T CellsCd4 T Cell ActivationImmune Checkpoint Inhibitor TherapyImmune Effector MoleculesInhibitory Checkpoint SignalingLatency Reversal TherapyProgrammed Cell Death Protein 1 (Pd-1) PathwayReservoir Persistence
Abstract HIV persists in latently infected CD4 + T cells during antiretroviral therapy (ART). Immune checkpoint molecules, including PD-1, are preferentially expressed at the surface of persistently infected cells. However, whether PD-1 plays a functional role in HIV latency and reservoir persistence remains unknown. Using CD4 + T cells from HIV-infected individuals, we show that the engagement of PD-1 inhibits viral production at the transcriptional level and abrogates T-cell receptor (TCR)-induced HIV reactivation in latently infected cells. Conversely, PD-1 blockade with the monoclonal antibody pembrolizumab enhances HIV production in combination with the latency reversing agent bryostatin without increasing T cell activation. Our results suggest that the administration of immune checkpoint blockers to HIV-infected individuals on ART may facilitate latency disruption.
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