Department of Medicine, Division of Rheumatic and Autoimmune Diseases, Center for Immunology, University of Minnesota, Minneapolis, Minnesota, USA.
Ann N Y Acad Sci. 2011 Jan;1217:45-59. doi: 10.1111/j.1749-6632.2010.05919.x.
Programmed death-1 (PD-1) is a surface receptor critical for the regulation of T cell function during immunity and tolerance. PD-1 interactions with its ligands PD-L1 and PD-L2 inhibit T cell effector functions in an antigen-specific manner. This paper examines the role of PD-1 in limiting autoreactivity and establishing self-tolerance and discusses the hypothesis that PD-1 ligand (PD-L) expression both spatially and temporally dictates the fate of self-reactive T cells during the breakdown of peripheral tolerance and development of autoimmunity. We focus our discussion on the role of PD-1/PD-L interactions during peripheral tolerance, the differential role for PD-L1 and PD-L2 in response to environmental or self-antigens, and the impact of PD-1 signaling on dynamic T cell motility and the T cell receptor (TCR) stop signal. Finally, we discuss the potential to selectively target the PD-1 pathway therapeutically to alter T cell function during autoimmunity.
程序性死亡受体-1（PD-1）是一种表面受体，在免疫和耐受过程中对 T 细胞功能的调节至关重要。PD-1 与其配体 PD-L1 和 PD-L2 的相互作用以抗原特异性的方式抑制 T 细胞效应功能。本文探讨了 PD-1 在限制自身反应性和建立自身耐受性中的作用，并提出了这样的假设，即 PD-1 配体（PD-L）的表达在时空上决定了自身反应性 T 细胞在外周耐受破坏和自身免疫发展过程中的命运。我们将讨论的重点放在 PD-1/PD-L 相互作用在外周耐受中的作用、PD-L1 和 PD-L2 在应对环境或自身抗原中的不同作用，以及 PD-1 信号对 T 细胞运动性和 T 细胞受体（TCR）停止信号的影响。最后，我们讨论了有选择性地靶向 PD-1 途径进行治疗以改变自身免疫过程中 T 细胞功能的潜力。
