Sawant Deepali V, Vignali Dario A A
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Immunol Rev. 2014 May;259(1):173-91. doi: 10.1111/imr.12173.
Regulatory T cells (Tregs) prevail as a specialized cell lineage that has a central role in the dominant control of immunological tolerance and maintenance of immune homeostasis. Thymus-derived Tregs (tTregs) and their peripherally induced counterparts (pTregs) are imprinted with unique Forkhead box protein 3 (Foxp3)-dependent and independent transcriptional and epigenetic characteristics that bestows on them the ability to suppress disparate immunological and non-immunological challenges. Thus, unidirectional commitment and the predominant stability of this regulatory lineage is essential for their unwavering and robust suppressor function and has clinical implications for the use of Tregs as cellular therapy for various immune pathologies. However, recent studies have revealed considerable heterogeneity or plasticity in the Treg lineage, acquisition of alternative effector or hybrid fates, and promotion rather than suppression of inflammation in extreme contexts. In addition, the absolute stability of Tregs under all circumstances has been questioned. Since these observations challenge the safety and efficacy of human Treg therapy, the issue of Treg stability versus plasticity continues to be enthusiastically debated. In this review, we assess our current understanding of the defining features of Foxp3(+) Tregs, the intrinsic and extrinsic cues that guide development and commitment to the Treg lineage, and the phenotypic and functional heterogeneity that shapes the plasticity and stability of this critical regulatory population in inflammatory contexts.
调节性T细胞（Tregs）作为一种特殊的细胞谱系占主导地位，在免疫耐受的主要控制和免疫稳态的维持中发挥核心作用。胸腺来源的Tregs（tTregs）及其外周诱导的对应物（pTregs）具有独特的依赖叉头框蛋白3（Foxp3）和不依赖Foxp3的转录及表观遗传特征，这些特征赋予它们抑制不同免疫和非免疫挑战的能力。因此，这种调节性谱系的单向定向和主要稳定性对于其坚定不移且强大的抑制功能至关重要，并且对于将Tregs用作各种免疫疾病的细胞疗法具有临床意义。然而，最近的研究揭示了Treg谱系中存在相当大的异质性或可塑性、获得替代效应或混合命运，以及在极端情况下促进而非抑制炎症。此外，Tregs在所有情况下的绝对稳定性也受到了质疑。由于这些观察结果挑战了人类Treg疗法的安全性和有效性，Treg稳定性与可塑性的问题仍在热烈讨论中。在这篇综述中，我们评估了我们目前对Foxp3(+) Tregs的定义特征、指导Treg谱系发育和定向的内在和外在线索，以及在炎症环境中塑造这一关键调节群体可塑性和稳定性的表型和功能异质性的理解。
