Hypoxia-inducible factors enhance CD8+ T cell effector responses to persistent antigen.

ABSTRACT: Cytolytic activity by CD8+ cytotoxic T lymphocytes (CTL) is a powerful tactic in the elimination of intracellular pathogens and tumor cells. The destructive capacity of CTL is progressively dampened during chronic infection - yet the environmental cues and molecular pathways controlling immune “exhaustion” remain unclear. We find CTL immunity is regulated by the central transcriptional response to hypoxia, mediated by the von-Hippel-Lindau/Hypoxia-Inducible-Factor (VHL/HIF) pathway. Deletion of VHL, the primary negative regulator of HIF, leads to lethal CTL-mediated immunopathology during chronic infection, and VHL-deficient CTL display enhanced control of persistent viral infection and neoplastic growth. We find HIF and oxygen influence expression of pivotal CTL transcription, effector an

ORGANISM(S): Mus musculus

SUBMITTER: Andrew Doedens 

PROVIDER: E-GEOD-50158 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress