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

Identifier:  imarina:9230387

Handle: https://hdl.handle.net/20.500.11797/imarina9230387

Authors:  Collins, DR; Urbach, JM; Racenet, ZJ; Arshad, U; Power, KA; Newman, RM; Mylvaganam, GH; Ly, NL; Lian, XD; Rull, A; Rassadkina, Y; Yanez, AG; Peluso, MJ; Deeks, SG; Vidal, F; Lichterfeld, M; Yu, XG; Gaiha, GD; Allen, TM; Walker, BD

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.