Piconese Silvia, Barnaba Vincenzo
Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Policlinico Umberto I, Viale del Policlinico 155, I-00161, Rome, Italy,
Adv Exp Med Biol. 2015;850:17-30. doi: 10.1007/978-3-319-15774-0_2.
Regulatory T cells (Tregs) encompass an array of immunosuppressive cells responsible for the protection against exacerbated immune responses and the maintenance of tissue homeostasis. Various Treg subtypes, normally resident within distinct lymphoid and non-lymphoid tissues, can be recruited and expanded during inflammation, possibly undergoing functional and molecular re-programming. Generally, two processes have been reported in different settings of type-1 response: i) Treg subpopulations acquiring the ability to specifically suppress Th1 cells (called Th1-suppressing Tregs), and ii) Treg subsets rather polarizing into IFN-γ-producing (called Th1-like) Tregs.Along the development of type-1 responses, Tregs are exposed to a variety of cytokines and other signals, exerting disparate activities. The combinatorial effects of typical Th1-driving cytokines, such as IL-12 (mostly produced by antigen-presenting cells during Th1 priming) and IFN-γ (mostly produced by pre-existing NK cells) lead to inhibition of Treg expansion and function, while promoting Th1-like Treg polarization. Conversely, cytokines produced at more advanced phases by Th1 effectors, such as IL-2, TNF-α and IFN-γ, promote Treg proliferation and/or Th1-suppressing Treg specialization. Some controversy exists around IL-27 and IFN-α, cytokines possibly released during bacterial or viral infections. Furthermore, cytokine signals can be finely tuned by the concomitant stimulation of costimulatory or coinhibitory receptors, such as OX40 and PD-1 respectively, within inflamed tissues.A model may be envisaged of an alternate Treg response to type-1 cytokines, being hampered or boosted by early or late phase cytokines, respectively. Such regulation would unleash the development of protective type-1 immunity while constraining exacerbated Th1 responses, possibly causing immunopathology.
调节性T细胞（Tregs）包含一系列免疫抑制细胞，负责防止免疫反应过度加剧并维持组织稳态。各种Treg亚型通常驻留在不同的淋巴组织和非淋巴组织中，在炎症期间可被招募和扩增，可能会经历功能和分子重编程。一般来说，在1型反应的不同情况下已报道了两个过程：i）Treg亚群获得特异性抑制Th1细胞的能力（称为Th1抑制性Tregs），以及ii）Treg亚群偏向分化为产生IFN-γ的（称为Th1样）Tregs。在1型反应的发展过程中，Tregs会接触到多种细胞因子和其他信号，从而发挥不同的作用。典型的Th1驱动细胞因子，如IL-12（主要由抗原呈递细胞在Th1启动期间产生）和IFN-γ（主要由预先存在的NK细胞产生）的联合作用会导致Treg扩增和功能受到抑制，同时促进Th1样Treg极化。相反，Th1效应细胞在更晚期产生的细胞因子，如IL-2、TNF-α和IFN-γ，会促进Treg增殖和/或Th1抑制性Treg特化。关于IL-27和IFN-α存在一些争议，这两种细胞因子可能在细菌或病毒感染期间释放。此外，细胞因子信号可通过炎症组织内共刺激或共抑制受体（如分别为OX40和PD-1）的伴随刺激进行微调。可以设想一个Treg对1型细胞因子的交替反应模型，分别受到早期或晚期细胞因子的阻碍或促进。这种调节将释放保护性1型免疫的发展，同时抑制过度加剧的Th1反应，可能导致免疫病理学。
