Metabolic Regulation of T Lymphocytes

By Nancie J. MacIver, Ryan D. Michalek, J. Rathmell. Annual Review of Immunology, 2013

1,189 citations recorded by the source corpus.

T cell activation leads to dramatic shifts in cell metabolism to protect against pathogens and to orchestrate the action of other immune cells. Quiescent T cells require predominantly ATP-generating processes, whereas proliferating effector T cells require high metabolic flux through growth-promoting pathways. Further, functionally distinct T cell subsets require distinct energetic and biosynthetic pathways to support their specific functional needs. Pathways that control immune cell function and metabolism are intimately linked, and changes in cell metabolism at both the cell and system levels have been shown to enhance or suppress specific T cell functions. As a result of these findings, cell metabolism is now appreciated as a key regulator of T cell function specification and fate. This review discusses the role of cellular metabolism in T cell development, activation, differentiation, and function to highlight the clinical relevance and opportunities for therapeutic interventions that may be used to disrupt immune pathogenesis.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/8d110718a764dbe03b95b6c4545bd647ab19b79a

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Citations in the corpus

Unraveling the Complex Interplay Between T Cell Metabolism and Function (2018, background): “High ROS in the TME can lead to apoptosis of Tregs, accompanied by release of ATP from dying cells.”
A transcriptionally and functionally distinct PD-1+ CD8+ T cell pool with predictive potential in non-small cell lung cancer treated with PD-1 blockade (2018, neutral): “5 (2D1), -CD56 PE (CMSSB), - CD3 APC-eFluor780 (SK7), -Lag-3 FITC (3DS223H), -TIGIT PE (MBSA43), -2B4 FITC (eBioDM244), -CD137 FITC (4B4), -IL-2 PE (MQ1-17H12), -TNF-α APC (MAb11), - CD26 FITC (2A6), -CXCR5 Biotin (MU5UBEE), -ICOS FITC (ISA-3), -CD38 APC (HIT2), -Eomes eFluor660 (WD1928), -T-bet PE ”
T cell lipid peroxidation induces ferroptosis and prevents immunity to infection (2015, background): “TCR stimulation has been shown to induce production of discrete species of ROS (i.e., hydrogen peroxide and superoxide anion), involving a phagocyte type NADPH oxidase expressed by T cells and the FAS pathway (Devadas et al., of bacteria, whereas groups of mice undergoing primary infection were all ”
Glucose Metabolism Regulates T Cell Activation, Differentiation, and Functions (2014, background): “However, Neildez-Nguyen and colleagues have recently shown that higher expression of Glut1 is detected on mouse Tregs generated under hypoxic (5% O2) culture conditions compared to those cultured under ambient oxygen levels (21% O2) (50).”
Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function. (2013, neutral): “Recent findings have highlighted the importance of cellular metabolism in regulating CD8 + T cell differentiation and memory formation (9–12).”
Cell Adhesion Molecules and Their Roles and Regulation in the Immune and Tumor Microenvironment (2019, background): “In effector T cells, LFA-1 is up-regulated and constitutively activated, which contributes to the trafficking properties of these cells to peripheral tissues (63, 64).”
CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer. (2019, background): “A major characteristic of lymphocytes is their metabolic plasticity during activation and in response to changes in their surrounding environment (99).”
Phosphoenolpyruvate Is a Metabolic Checkpoint of Anti-tumor T Cell Responses (2015, background): “Activation of PI3K, Akt, and mTOR triggers the switch to anabolic metabolism by inducing transcription factors such as Myc and hypoxia-inducible factor 1 (HIF1) (MacIver et al., 2013; Wang et al., 2011a).”
Inflammatory T cell responses rely on amino acid transporter ASCT2 facilitation of glutamine uptake and mTORC1 kinase activation (2014, neutral): “Moreover, emerging evidence suggests that proper activation and differentiation of T cells are also influenced by other signals derived from the immune microenvironment, including metabolic stimuli (MacIver et al., 2013; van der Windt and Pearce, 2012; Waickman and Powell, 2012).”
Reactive gliosis and the multicellular response to CNS damage and disease (2014, neutral): “Similarly, T cells stimulated by different cytokines become polarized toward different activities, such as TH1, TReg, and TH17 cells, which can exert very different effects ranging from cell killing to participation in tissue repair (MacIver et al., 2013; Mills, 2011; Walsh and Kipnis, 2011).”
The Balance of Th17 versus Treg Cells in Autoimmunity (2018, background): “By contrast, Treg cells are catabolic; therefore, they metabolize fatty acids and amino acids, as well as glucose, and use oxidative phosphorylation to synthesize ATP [69].”
Foxp3 reprograms T cell metabolism to function in low glucose high lactate environments (2017, background): “It is possible to speculate that defects in Treg metabolism and ultimately loss of the Treg metabolic advantage in ischemic tissues can lead to autoimmune diseases such as systemic lupus erythematosus (MacIver et al., 2013).”
The Glucose Transporter Glut1 is Selectively Essential for CD4 T Cell Activation and Effector Function (2014, neutral): “These metabolic programs provide distinct metabolites (MacIver et al., 2013), signaling through the mammalian target of rapamycin complex 1 (mTORC1) pathway (Sinclair et al., 2013), and cytokine production (Cham and Gajewski, 2005; Chang et al., 2013).”