학술논문
Functional impairment of HIV-specific CD8+ T cells precedes aborted spontaneous control of viremia
Document Type
article
Author
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; Vidal, Francesc; Lichterfeld, Mathias; Yu, Xu G; Gaiha, Gaurav D; Allen, Todd M; Walker, Bruce D
Source
Immunity. 54(10)
Subject
Language
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.