Some aspects of CD8+ T-cell exhaustion are associated with altered T-cell mitochondrial features and ROS content in HIV infection
CDT Deguit, M Hough, R Hoh, M Krone… - JAIDS Journal of …, 2019 - journals.lww.com
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2019•journals.lww.com
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 …
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 …
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.
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