1. Functional impairment of HIV-specific CD8+ T cells precedes aborted spontaneous control of viremia
- Author
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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, and Walker, Bruce D
- Subjects
Adult ,Male ,human immunology ,Immunology ,HIV Infections ,CD8-Positive T-Lymphocytes ,Middle Aged ,CD8(+) T cell dysfunction ,Infectious Diseases ,Good Health and Well Being ,Recurrence ,Humans ,HIV/AIDS ,2.1 Biological and endogenous factors ,Female ,Viremia ,Aetiology ,Infection ,HIV control - Abstract
Spontaneous control of HIV infection has been repeatedly linked to antiviral CD8+ Tcells 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 Tcell effector functions became selectively and intrinsically impaired prior to aborted control. Longitudinal transcriptomic profiling of functionally impaired HIV-specific CD8+ Tcells 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+ Tcells also exhibited poor functionality during aborted control relative to durable control. Our results identify selective functional impairment of HIV-specific CD8+ Tcells as prognostic of impending aborted HIV control, with implications for clinical monitoring and immunotherapeutic strategies.
- Published
- 2021