San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Division of Regenerative Medicine, Stem Cells and Gene Therapy, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy,
Curr Top Microbiol Immunol. 2014;380:39-68. doi: 10.1007/978-3-662-43492-5_3.
T regulatory Type 1 (Tr1) cells are adaptive T regulatory cells characterized by the ability to secrete high levels of IL-10 and minimal amounts of IL-4 and IL-17. Recently, CD49b and LAG-3 have been identified as Tr1-cell-specific biomarkers in mice and humans. Tr1 cells suppress T-cell- and antigen-presenting cell- (APC) responses primarily via the secretion of IL-10 and TGF-β. In addition, Tr1 cells release granzyme B and perforin and kill myeloid cells. Tr1 cells inhibit T cell responses also via cell-contact dependent mechanisms mediated by CTLA-4 or PD-1, and by disrupting the metabolic state of T effector cells via the production of the ectoenzymes CD39 and CD73. Tr1 cells were first described in peripheral blood of patients who developed tolerance after HLA-mismatched fetal liver hematopoietic stem cell transplant. Since their discovery, Tr1 cells have been proven to be important in maintaining immunological homeostasis and preventing T-cell-mediated diseases. Furthermore, the possibility to generate and expand Tr1 cells in vitro has led to their utilization as cellular therapy in humans. In this chapter we summarize the unique and distinctive biological properties of Tr1 cells, the well-known and newly discovered Tr1-cell biomarkers, and the different methods to induce Tr1 cells in vitro and in vivo. We also address the role of Tr1 cells in infectious diseases, autoimmunity, and transplant rejection in different pre-clinical disease models and in patients. Finally, we highlight the pathological settings in which Tr1 cells can be beneficial to prevent or to cure the disease.
调节性 T 细胞 1 型（Tr1）是适应性调节性 T 细胞，其特征在于能够高水平分泌 IL-10 和极少数量的 IL-4 和 IL-17。最近，CD49b 和 LAG-3 已被鉴定为小鼠和人类 Tr1 细胞特异性生物标志物。Tr1 细胞主要通过分泌 IL-10 和 TGF-β来抑制 T 细胞和抗原呈递细胞（APC）的反应。此外，Tr1 细胞释放颗粒酶 B 和穿孔素并杀死髓样细胞。Tr1 细胞还通过 CTLA-4 或 PD-1 介导的细胞接触依赖机制，以及通过产生外切酶 CD39 和 CD73 来破坏 T 效应细胞的代谢状态来抑制 T 细胞反应。Tr1 细胞最初是在 HLA 错配的胎肝造血干细胞移植后产生耐受的患者外周血中描述的。自发现以来，Tr1 细胞已被证明在维持免疫稳态和预防 T 细胞介导的疾病方面具有重要作用。此外，体外生成和扩增 Tr1 细胞的可能性导致它们在人类中被用作细胞疗法。在本章中，我们总结了 Tr1 细胞的独特和独特的生物学特性、众所周知和新发现的 Tr1 细胞生物标志物，以及体外和体内诱导 Tr1 细胞的不同方法。我们还讨论了 Tr1 细胞在不同临床前疾病模型和患者中的感染性疾病、自身免疫和移植排斥中的作用。最后，我们强调了 Tr1 细胞在预防或治疗疾病方面有益的病理环境。
