PD-1 signaling affects cristae morphology and leads to mitochondrial dysfunction in human CD8⁺ T lymphocytes.

ABSTRACT:

Background

Binding of the programmed death-1 (PD-1) receptor to its ligands (PD-L1/2) transduces inhibitory signals that promote exhaustion of activated T cells. Blockade of the PD-1 pathway is widely used for cancer treatment, yet the inhibitory signals transduced by PD-1 in T cells remain elusive.

Methods

Expression profiles of human CD8⁺ T cells in resting, activated (CD3 + CD28) and PD-1-stimulated cells (CD3 + CD28 + PD-L1-Fc) conditions were evaluated by RNA-seq. Bioinformatic analyses were used to identify signaling pathways differentially regulated in PD-1-stimulated cells. Metabolic analyses were performed with SeaHorse technology, and mitochondrial ultrastructure was determined by transmission electron microscopy. PD-1-regulated mitochondrial genes were

SUBMITTER: Ogando J 

PROVIDER: S-EPMC6567413 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature