Regulatory T (T_reg) cells are a suppressive subset of CD4⁺ T cells that maintain immune homeostasis and restrain inflammation. Three decades after their discovery, the promise of strategies to harness T_reg cells for therapy has never been stronger. Multiple clinical trials seeking to enhance endogenous T_reg cells or deliver them as a cell-based therapy have been performed and hint at signs of success, as well as to important limitations and unanswered questions. Strategies to deplete T_reg cells in cancer are also in active clinical testing. Furthermore, multi-dimensional methods to interrogate the biology of T_reg cells are leading to a refined understanding of T_reg cell biology and new approaches to harness tissue-specific functions for therapy. A new generation of T_reg cell clinical trials is now being fuelled by advances in nanomedicine and synthetic biology, seeking more precise ways to tailor T_reg cell function. This Review will discuss recent advances in our understanding of human T_reg cell biology, with a focus on mechanisms of action and strategies to assess outcomes of T_reg cell-targeted therapies. It highlights results from recent clinical trials aiming to enhance or inhibit T_reg cell activity in a variety of diseases, including allergy, transplantation, autoimmunity and cancer, and discusses ongoing strategies to refine these approaches.

调节性 T （T_reg） 细胞是 CD4⁺ T 细胞的抑制性亚群，可维持免疫稳态并抑制炎症。在他们被发现三十年后，利用 T_reg 细胞进行治疗的策略的前景从未如此强烈。已经进行了多项临床试验，旨在增强内源性_{T reg} 细胞或将其作为基于细胞的疗法提供，并暗示了成功的迹象，以及重要的局限性和未解之谜。在癌症中消耗 T_reg 细胞的策略也正在进行积极的临床试验。此外，询问 T_reg 细胞生物学的多维方法正在导致对 T_reg 细胞生物学的精细理解和利用组织特异性功能进行治疗的新方法。纳米医学和合成生物学的进步正在推动新一代 T_reg 细胞临床试验，寻求更精确的方法来定制 T_reg 细胞功能。本综述将讨论我们对人类 T_reg 细胞生物学理解的最新进展，重点关注评估 T_reg 细胞靶向治疗结果的作用机制和策略。它重点介绍了最近旨在增强或抑制多种疾病（包括过敏、移植、自身免疫和癌症）中 T_reg 细胞活性的临床试验的结果，并讨论了改进这些方法的持续策略。