| Literature DB >> 34496223 |
David R Collins1, Jonathan M Urbach2, Zachary J Racenet2, Umar Arshad2, Karen A Power2, Ruchi M Newman2, Geetha H Mylvaganam1, Ngoc L Ly2, Xiaodong Lian3, Anna Rull4, Yelizaveta Rassadkina3, Adrienne G Yanez1, Michael J Peluso5, Steven G Deeks5, Francesc Vidal4, Mathias Lichterfeld3, Xu G Yu3, Gaurav D Gaiha6, Todd M Allen2, Bruce D Walker7.
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.Entities:
Keywords: CD8(+) T cell dysfunction; HIV control; human immunology
Mesh：
Year: 2021 PMID： 34496223 PMCID： PMC8516715 DOI： 10.1016/j.immuni.2021.08.007
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 43.474