Investigating the role of Bcl-2 protein, Noxa, in the metabolic reprogramming, differentiation and apoptosis of CD8+ T cells during the immune response

Abstract

Human Noxa was previously shown to have both pro-apoptotic and pro-growth functions in leukemic and primary T cells. Noxa was also shown to be required for the switch to glutamine metabolism of antigen stimulated CD8+ T cells. Our studies show that Noxa is consistently induced in normal human CD8+T cells upon stimulation and remains highly expressed during differentiation and through the onset of apoptosis. Memory-like CD8+ T cells recovered at the end of the immune response no longer express Noxa but exhibit robust induction of the protein upon re-stimulation. CD8+ T cells lacking Noxa expression showed an overall reduced dependence on glutamine and higher viability at the end of the immune response. Our studies have offered valuable insights into metabolic pathways that regulate cell fate in human CD8+ T lymphocytes and a deeper understanding of Noxa’s role in regulating T cell metabolism and will help evaluate Noxa’s potential for immunotherapy.