title: Nutrients and the microenvironment to feed a T cell army.
abstract: T cells have dramatic functional and proliferative shifts in the course of maintaining immune protection from pathogens and cancer. To support these changes, T cells undergo metabolic reprogramming upon stimulation and again after antigen clearance. Depending on the extrinsic cell signals, T cells can differentiate into functionally distinct subsets that utilize and require diverse metabolic programs. Effector T cells (Teff) enhance glucose and glutamine uptake, whereas regulatory T cells (Treg) do not rely on significant rates of glycolysis. The dependence of these subsets on specific metabolic programs makes T cells reliant on these signaling pathways and nutrients. Metabolic pathways, such as those regulated by mTOR and Myc, augment T cell glycolysis and glutaminolysis programs to promote T cell activity. These pathways respond to signals and control metabolism through both transcriptional or post-transcriptional mechanisms. Epigenetic modifications also play an important role by stabilizing the transcription factors that define subset specific reprogramming. In addition, circadian rhythm cycling may also influence energy use, immune surveillance, and function of T cells. In this review, we focus on the metabolic and nutrient requirements of T cells, and how canonical pathways of growth and metabolism regulate nutrients that are essential for T cell function.
authors.affiliation: Department of Pathology, Microbiology, and Immunology, and Cancer Biology, Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN 37232, United States.
authors.forename: Marc O
authors.initials: MO
authors.lastname: Johnson
authors.affiliation: Department of Pathology, Microbiology, and Immunology, and Cancer Biology, Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN 37232, United States.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Siska
authors.affiliation: Department of Pathology, Microbiology, and Immunology, and Cancer Biology, Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN 37232, United States.
authors.forename: Diana C
authors.initials: DC
authors.lastname: Contreras
authors.affiliation: Department of Pathology, Microbiology, and Immunology, and Cancer Biology, Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN 37232, United States. Electronic address: jeff.rathmell@vanderbilt.edu.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Rathmell
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001683:Biological Clocks / Q000235:genetics / Q000276:immunology; D060833:Cellular Microenvironment / Q000276:immunology; D004734:Energy Metabolism; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
chemical_list: D005973:Glutamine; D005947:Glucose
keywords: Circadian rhythms; Epigenetics; Glut1; Glutamine; T cell metabolism; mTOR