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

David R Collins; Jonathan M Urbach; Zachary J Racenet; Umar Arshad; Karen A Power; Ruchi M Newman; Geetha H Mylvaganam; Ngoc L Ly; Xiaodong Lian; Anna Rull; Yelizaveta Rassadkina; Adrienne G Yanez; Michael J Peluso; Steven G Deeks; Francesc Vidal; Mathias Lichterfeld; Xu G Yu; Gaurav D Gaiha; Todd M Allen; Bruce D Walker

doi:10.1016/j.immuni.2021.08.007

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

Immunity. 2021 Oct 12;54(10):2372-2384.e7. doi: 10.1016/j.immuni.2021.08.007. Epub 2021 Sep 7.

Authors

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

Affiliations

¹ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
² Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
³ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.
⁴ Joan XXIII University Hospital, Pere Virgili Institute (IISPV), Rovira i Virgili University, Tarragona, Spain.
⁵ Division of HIV, Infectious Diseases and Global Medicine, University of California, San Francisco, CA, USA.
⁶ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.
⁷ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA; Institute for Medical Engineering and Sciences and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: bwalker@mgh.harvard.edu.

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.

Keywords: CD8(+) T cell dysfunction; HIV control; human immunology.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
CD8-Positive T-Lymphocytes / immunology*
Female
HIV Infections / immunology*
HIV Infections / virology*
Humans
Male
Middle Aged
Recurrence
Viremia / immunology*
Viremia / virology*

Abstract

Publication types

MeSH terms

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