Projects per year
Metabolic and nutrient-sensing pathways play an important role in controlling the efficacy of effector T cells. Oxygen is a critical regulator of cellular metabolism. However, during immune responses T cells must function in oxygen-deficient, or hypoxic, environments. Here, we used high resolution mass spectrometry to investigate how the proteome of primary murine CD8+ cytotoxic T lymphocytes (CTLs) is reconfigured in response to hypoxia in vitro. We identified and quantified over 7,600 proteins and discovered that hypoxia increased the abundance of a selected number of proteins in CTLs. This included glucose transporters, metabolic enzymes, transcription factors, cytolytic effector molecules, checkpoint receptors and adhesion molecules. While some of these proteins may augment the effector functions of CTLs, others may limit their cytotoxicity. Moreover, we determined that hypoxia could inhibit IL-2-induced proliferation cues and antigen-induced pro-inflammatory cytokine production in CTLs. These data provide a comprehensive resource for understanding the magnitude of the CTL response to hypoxia and emphasise the importance of oxygen-sensing pathways for controlling CD8+ T cells. Additionally, this study provides new understanding about how hypoxia may promote the effector function of CTLs, while contributing to their dysfunction in some contexts.
|Number of pages||18|
|Journal||Frontiers in Immunology|
|Publication status||Published - 17 Sept 2021|
- CD8 T cells
- cytotoxic lymphocytes
- oxygen sensing
- quantitative proteomics
ASJC Scopus subject areas
- Immunology and Allergy
FingerprintDive into the research topics of 'Quantitative Analyses Reveal How Hypoxia Reconfigures the Proteome of Primary Cytotoxic T Lymphocytes'. Together they form a unique fingerprint.
- 1 Active
Fingerprints Proteomics FacilityCentre for Advanced Scientific Technologies
Flow Cytometry and Cell SortingCentre for Advanced Scientific Technologies