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

Collins, David R.; Urbach, Jonathan M.; Racenet, Zachary J.; Arshad, Umar; Power, Karen A.; Newman, Ruchi M.; Mylvaganam, Geetha H.; Ly, Ngoc L.; Lian, Xiaodong; Rull, Anna; Rassadkina, Yelizaveta; Yanez, Adrienne G.; Peluso, Michael J.; Deeks, Steven G.;

IMMUNITY
2021
VL / 54 - BP / 2372 - EP / +
abstract
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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