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.


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*