Some Aspects of CD8+ T-Cell Exhaustion Are Associated With Altered T-Cell Mitochondrial Features and ROS Content in HIV Infection

J Acquir Immune Defic Syndr. 2019 Oct 1;82(2):211-219. doi: 10.1097/QAI.0000000000002121.


Background: Reversing or preventing T-cell exhaustion is an important treatment goal in the context of HIV disease; however, the mechanisms that regulate HIV-specific CD8 T-cell exhaustion are incompletely understood. Since mitochondrial mass (MM), mitochondrial membrane potential (MMP), and cellular reactive oxygen species (ROS) content are altered in exhausted CD8 T cells in other settings, we hypothesized that similar lesions may arise in HIV infection.

Methods: We sampled cryopreserved peripheral blood mononuclear cells from HIV-uninfected (n = 10) and HIV-infected participants with varying levels and mechanisms of viral control: viremic (VL > 2000 copies/mL; n = 8) or aviremic (VL < 40 copies/mL) due to antiretroviral therapy (n = 11) or natural control (n = 9). We characterized the MM, MMP, and ROS content of bulk CD8 T cells and MHC class I tetramer+ HIV-specific CD8 T cells by flow cytometry.

Results: We observed higher MM, MMP, and ROS content across bulk effector-memory CD8 T-cell subsets in HIV-infected compared with HIV-uninfected participants. Among HIV-specific CD8 T cells, these features did not vary by the extent or mechanism of viral control but were significantly altered in cells displaying characteristics associated with exhaustion (eg, high PD-1 expression, low CD127 expression, and impaired proliferative capacity).

Conclusions: While we did not find that control of HIV replication in vivo correlates with the CD8 T-cell MM, MMP, or ROS content, we did find that some features of CD8 T-cell exhaustion are associated with alterations in mitochondrial state. Our findings support further studies to probe the relationship between mitochondrial dynamics and CD8 T-cell functionality in HIV infection.

Publication types

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

MeSH terms

  • CD8-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / ultrastructure
  • HIV Infections / immunology*
  • HIV Infections / metabolism
  • Humans
  • Interleukin-7 Receptor alpha Subunit / analysis
  • Lymphocyte Activation
  • Membrane Potential, Mitochondrial
  • Mitochondria / metabolism*
  • Programmed Cell Death 1 Receptor / analysis
  • Reactive Oxygen Species / metabolism*
  • Viremia / immunology*


  • Interleukin-7 Receptor alpha Subunit
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Reactive Oxygen Species