The Ups and Downs of Metabolism during the Lifespan of a T Cell

Abstract

Understanding the various mechanisms that govern the development, activation, differentiation, and functions of T cells is crucial as it could provide opportunities for therapeutic interventions to disrupt immune pathogenesis. Immunometabolism is one such area that has garnered significant interest in the recent past as it has become apparent that cellular metabolism is highly dynamic and has a tremendous impact on the ability of T cells to grow, activate, and differentiate. In each phase of the lifespan of a T-cell, cellular metabolism has to be tailored to match the specific functional requirements of that phase. Resting T cells rely on energy-efficient oxidative metabolism but rapidly shift to a highly glycolytic metabolism upon activation in order to meet the bioenergetically demanding process of growth and proliferation. However, upon antigen clearance, T cells return to a more quiescent oxidative metabolism to support T cell memory generation. In addition, each helper T cell subset engages distinct metabolic pathways to support their functional needs. In this review, we provide an overview of the metabolic changes that occur during the lifespan of a T cell and discuss several important studies that provide insights into the regulation of the metabolic landscape of T cells and how they impact T cell development and function.

The effects of graded calorie restriction XVII: Multitissue metabolomics reveals synthesis of carnitine and NAD, and tRNA charging as key pathways

“…Another molecule that was up-regulated in this pathway was AMP. This molecule contributes to AMP-activated protein kinase (AMPK) activation, an enzyme and key nutrient sensor with the ability to regulate whole-body metabolism since it maximizes ATP generation by promoting catabolic pathways inhibiting anabolic processes that consume ATP (54). During CR, AMPK becomes activated in diverse tissues, including the heart, liver, skeletal muscle, and hypothalamus (55,56).…”

Pharmacological Inhibition of Glutaminase 1 Normalized the Metabolic State and CD4+ T Cell Response in Sjogren’s Syndrome

“…For example, upon activation, CD4+ T cells selectively elevate glycolysis, a process of glucose metabolism that takes up glucose into cells and converts it into pyruvate to fulfill the massive energy demand as the priming stages. Additionally, glutaminolysis, a process of amino acid metabolism that converts glutamine, a commonly existing animo-acid product, into glutaminate and alpha ketoglutarate ( α -KG), which then enters the tricarboxylic acid (TCA) cycle [ 8 , 10 ], was also activated to support the proliferation of CD4+ T cells. Targeting these processes has been demonstrated to alter the progression of several autoimmune diseases, including SS [ 11 , 12 ].…”

The Immunometabolic Roles of Various Fatty Acids in Macrophages and Lymphocytes

“…Clonal expansion of T cells following rearrangement of the T cell receptor (TCR), which occurs as part of T cell maturation, requires energy and this is generated by glycolysis with glucose influx into the cells involving glucose transporter (GLUT)-1 [10]. Conversely, naïve T cells themselves revert to a low-energy state with a significant reduction in glucose transport [20].…”