Guardians of silence: transcriptional networks in T cell quiescence

The maintenance of quiescence in T cells plays a pivotal role in averting undesired immune reactions and fostering immune homeostasis. Upon receiving external signals of cognate antigen and costimulatory molecules, T cells escape a quiescent state and rapidly proliferate within an exceedingly short timeframe. Nevertheless, for the majority of their lifespan, T cells remain inactive before stimulation, yet they are highly poised to future activation, implicating the presence of dynamic and intricate regulatory processes in a seemingly dormant state. While numerous extrinsic cues have been identified to induce T cell activation from a quiescence currently, intrinsic mechanisms governing T cell quiescence have received limited attention. Here we provide a comprehensive overview of multiple factors involved in T cell quiescence and their molecular mechanisms mainly in the context of transcriptional and post-transcriptional regulation. Given the intricate interplay between the control of T cell quiescence and a variety of diseases including autoimmunity, exhaustion and even tumor control, a thorough understanding of current insights into T cell quiescence affords us a valuable opportunity to advance our comprehension of T cell biology.