Programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, deliver inhibitory signals that regulate the balance between T cell activation, tolerance, and immunopathology. Immune responses to foreign and self-antigens require specific and balanced responses to clear pathogens and tumors and yet maintain tolerance. Induction and maintenance of T cell tolerance requires PD-1, and its ligand PD-L1 on nonhematopoietic cells can limit effector T cell responses and protect tissues from immune-mediated tissue damage. The PD-1:PD-L pathway also has been usurped by microorganisms and tumors to attenuate antimicrobial or tumor immunity and facilitate chronic infection and tumor survival. The identification of B7-1 as an additional binding partner for PD-L1, together with the discovery of an inhibitory bidirectional interaction between PD-L1 and B7-1, reveals new ways the B7:CD28 family regulates T cell activation and tolerance. In this review, we discuss current understanding of the immunoregulatory functions of PD-1 and its ligands and their therapeutic potential.

中文翻译：

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PD-1及其配体在耐受和免疫中的作用。

程序性死亡 1 (PD-1) 及其配体 PD-L1 和 PD-L2 传递抑制信号，调节 T 细胞激活、耐受和免疫病理学之间的平衡。对外来和自身抗原的免疫反应需要对清除病原体和肿瘤产生特异性和平衡的反应，同时保持耐受性。T细胞耐受性的诱导和维持需要PD-1，其非造血细胞上的配体PD-L1可以限制效应T细胞反应并保护组织免受免疫介导的组织损伤。PD-1:PD-L 通路也已被微生物和肿瘤侵占，以减弱抗菌或肿瘤免疫力并促进慢性感染和肿瘤存活。B7-1 作为 PD-L1 的额外结合伴侣的鉴定，以及 PD-L1 和 B7-1 之间抑制性双向相互作用的发现，揭示了 B7:CD28 家族调节 T 细胞激活和耐受的新方式。在这篇综述中，我们讨论了目前对 PD-1 及其配体的免疫调节功能及其治疗潜力的理解。