[PDF][PDF] Functional impairment of HIV-specific CD8+ T cells precedes aborted spontaneous control of viremia

DR Collins, JM Urbach, ZJ Racenet, U Arshad… - Immunity, 2021 - cell.com
DR Collins, JM Urbach, ZJ Racenet, U Arshad, KA Power, RM Newman, GH Mylvaganam…
Immunity, 2021cell.com
Spontaneous control of HIV infection has been repeatedly linked to antiviral CD8+ T cells
but is not always permanent. To address mechanisms of durable and aborted control of
viremia, we evaluated immunologic and virologic parameters longitudinally among 34 HIV-
infected subjects with differential outcomes. Despite sustained recognition of autologous
virus, HIV-specific proliferative and cytolytic T cell effector functions became selectively and
intrinsically impaired prior to aborted control. Longitudinal transcriptomic profiling of …
Summary
Spontaneous control of HIV infection has been repeatedly linked to antiviral CD8+ T cells but is not always permanent. To address mechanisms of durable and aborted control of viremia, we evaluated immunologic and virologic parameters longitudinally among 34 HIV-infected subjects with differential outcomes. Despite sustained recognition of autologous virus, HIV-specific proliferative and cytolytic T cell effector functions became selectively and intrinsically impaired prior to aborted control. Longitudinal transcriptomic profiling of functionally impaired HIV-specific CD8+ T cells revealed altered expression of genes related to activation, cytokine-mediated signaling, and cell cycle regulation, including increased expression of the antiproliferative transcription factor KLF2 but not of genes associated with canonical exhaustion. Lymphoid HIV-specific CD8+ T cells also exhibited poor functionality during aborted control relative to durable control. Our results identify selective functional impairment of HIV-specific CD8+ T cells as prognostic of impending aborted HIV control, with implications for clinical monitoring and immunotherapeutic strategies.
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