Laboratory of Molecular Immunology and The Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Nat Rev Immunol. 2018 Oct;18(10):648-659. doi: 10.1038/s41577-018-0046-y.
IL-2 was first identified as a growth factor capable of driving the expansion of activated human T cell populations. In the more than 40 years since its discovery, a tremendous amount has been learned regarding the mechanisms that regulate the expression of both IL-2 and its cell surface receptor, its mechanisms of signalling and its range of biological actions. More recently, the mechanisms by which IL-2 regulates CD4 T cell differentiation and function have been elucidated. IL-2 also regulates the effector and memory responses of CD8 T cells, and the loss of IL-2 or responsiveness to IL-2 at least in part explains the exhausted phenotype that occurs during chronic viral infections and in tumour responses. These basic mechanistic studies have led to the therapeutic ability to manipulate the action of IL-2 on regulatory T (T) cells for the treatment of autoimmune disease and on CD8 T cells for immunotherapy of cancer. IL-2 can have either positive or deleterious effects, and we discuss here recent ideas and approaches for manipulating the actions and overall net effects of IL-2 in disease settings, including cancer.
白细胞介素 2（IL-2）最初被鉴定为一种能够促进激活的人类 T 细胞群体扩增的生长因子。自发现以来的 40 多年里，人们已经了解了大量关于调节 IL-2 及其细胞表面受体表达、信号转导机制及其广泛生物学作用的机制。最近，阐明了 IL-2 调节 CD4 T 细胞分化和功能的机制。IL-2 还调节 CD8 T 细胞的效应器和记忆应答，IL-2 的缺失或对 IL-2 的反应性至少部分解释了慢性病毒感染和肿瘤反应中出现的耗竭表型。这些基础的机制研究导致了治疗性干预的能力，即在自身免疫疾病中操纵 IL-2 对调节性 T（T）细胞的作用，以及在癌症的免疫治疗中对 CD8 T 细胞的作用。IL-2 可能产生积极或有害的影响，我们在这里讨论了在疾病环境中操纵 IL-2 的作用和整体净效应的最新想法和方法，包括癌症。
