This Review explores the interplay between T cell activation and cell metabolism and highlights how metabolites serve two pivotal functions in shaping the immune response. Traditionally, T cell activation has been characterized by T cell antigen receptor–major histocompatibility complex interaction (signal 1), co-stimulation (signal 2) and cytokine signaling (signal 3). However, recent research has unveiled the critical role of metabolites in this process. Firstly, metabolites act as signal propagators that aid in the transmission of core activation signals, such as specific lipid species that are crucial at the immune synapse. Secondly, metabolites also function as unique signals that influence immune differentiation pathways, such as amino acid-induced mTORC1 signaling. Metabolites also play a substantial role in epigenetic remodeling, by directly modifying histones, altering gene expression and influencing T cell behavior. This Review discusses how T cells integrate nutrient sensing with activating stimuli to shape their differentiation and sensitivity to metabolites. We underscore the integration of immunological and metabolic inputs in T cell function and suggest that metabolite availability is a fundamental determinant of adaptive immune responses.

这篇综述探讨了 T 细胞激活和细胞代谢之间的相互作用，并强调了代谢物如何在塑造免疫反应中发挥两个关键功能。传统上，T 细胞激活的特点是 T 细胞抗原受体与主要组织相容性复合物相互作用（信号 1）、共刺激（信号 2）和细胞因子信号传导（信号 3）。然而，最近的研究揭示了代谢物在此过程中的关键作用。首先，代谢物充当信号传播者，有助于传递核心激活信号，例如对免疫突触至关重要的特定脂质种类。其次，代谢物还充当影响免疫分化途径的独特信号，例如氨基酸诱导的 mTORC1 信号传导。代谢物还通过直接修饰组蛋白、改变基因表达和影响 T 细胞行为，在表观遗传重塑中发挥重要作用。这篇综述讨论了 T 细胞如何将营养感应与激活刺激相结合，以塑造其分化和对代谢物的敏感性。我们强调 T 细胞功能中免疫学和代谢输入的整合，并表明代谢物的可用性是适应性免疫反应的基本决定因素。