ArticleImmunoHorizons2020
Differential Fuel Requirements of Human NK Cells and Human CD8 T Cells: Glutamine Regulates Glucose Uptake in Strongly Activated CD8 T Cells.
Article in ImmunoHorizons, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Machine learning-based identification of a metabolic cell death gene signature for assessing disease activity and immunological landscape in inflammatory bowel disease.Scientific reports · 2026Article
- Metabolic tracing reveals IL-2 driven glutaminolysis and de novo pyrimidine synthesis in human natural killer cells.The Journal of biological chemistry · 2026Article
- Molecular and cellular landscapes of the immune microenvironment and multiomic biomarker-sets in platinum-resistant recurrent ovarian cancers.Journal of ovarian research · 2026Review
- Multidimensional plasticity of natural killer cells in tumours.Cell death & disease · 2025Review
- Glutamine and allergic rhinitis: A bidirectional two-sample Mendelian randomization study.Medicine · 2025Article
- Energy metabolism in health and diseases.Signal transduction and targeted therapy · 2025Review
- Glutamine and cancer: metabolism, immune microenvironment, and therapeutic targets.Cell communication and signaling : CCS · 2025Review
- Polyamines: the pivotal amines in influencing the tumor microenvironment.Discover oncology · 2024Review
- Fatty acid oxidation fuels natural killer cell responses against infection and cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A glutamine tug-of-war between cancer and immune cells: recent advances in unraveling the ongoing battle.Journal of experimental & clinical cancer research : CR · 2024Review
- Crosstalk between arginine, glutamine, and the branched chain amino acid metabolism in the tumor microenvironment.Frontiers in oncology · 2023Review
- Challenges to the broad application of allogeneic natural killer cell immunotherapy of cancer.Stem cell research & therapy · 2022Review
- Review
- The mTORC1 Signaling Support Cellular Metabolism to Dictate Decidual NK Cells Function in Early Pregnancy.Frontiers in immunology · 2022Article
- Activated Natural Killer Cells Withstand the Relatively Low Glucose Concentrations Found in the Bone Marrow of Multiple Myeloma Patients.Frontiers in oncology · 2021Article
- The Appalachian Career Training in Oncology (ACTION) Program: Preparing Appalachian Kentucky High School and Undergraduate Students for Cancer Careers.Journal of STEM outreach · 2021Article
- Glutamine Metabolism in Cancer.Advances in experimental medicine and biology · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
CD8 T cells and NK cells are the two major cytotoxic lymphocytes that carry out cell-mediated immunity and regulate other immune responses. However, we do not completely understand human CD8 T cell and NK cell metabolic requirements and they have not been compared in the same experiments. We activated human CD8 T cells by two anti-CD3/CD28 mAb methods, and we stimulated both CD8 T cells and NK cells with IL-12/IL-18. When glucose (Glc) could not be used, human CD8 T cells either died or became hypofunctional, depending upon the anti-CD3/CD28 activation method. In contrast, Glc starvation did not decrease the percentage of IL-12/IL-18-stimulated human NK cells that made IFN-γ. NK cells were relatively fuel resilient and used Glc, glutamine (Gln), fatty acid, or acetate to power IFN-γ expression. Surprisingly, strongly activated human CD8 T cells required Gln for glycolysis and Glc uptake. We showed that human CD8 T cells regulate Glc uptake by a novel mechanism related to the TXNIP pleiotropic protein. These conditions may be relevant to septic patients who have high blood Glc but low Gln. Under the conditions tested, Gln did not change human NK cell TXNIP expression. Our experiments reveal fundamental differences in human CD8 T cell and NK cell metabolism and the fuels needed for IFN-γ production.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.