Okazaki Taku, Honjo Tasuku
21st Century Center of Excellence Program, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto, 606-8501, Japan.
Trends Immunol. 2006 Apr;27(4):195-201. doi: 10.1016/j.it.2006.02.001. Epub 2006 Feb 24.
Since the first observation of spontaneous autoimmune diseases in programmed cell death 1 (PD-1) knockout mice, PD-1 has been postulated to have essential roles in the regulation of autoimmunity but the precise mechanism was largely unknown. Recent studies clearly demonstrated that PD-1 has dual roles in immunological tolerance: induction and maintenance of peripheral tolerance. PD-1 ligands (PD-Ls) on antigen-presenting cells have been shown to switch off autoreactive T cells and induce peripheral tolerance, whereas those on parenchymal cells prevent tissue destruction by suppressing effector T cells to maintain tolerance. In addition, PD-1 and other immuno-inhibitory receptors have been shown to collaborate in the regulation of tolerance. Here, we review recent studies on the role of PD-1 in immunological tolerance and discuss possible clinical applications of PD-1 manipulation.
自从在程序性细胞死亡蛋白1（PD-1）基因敲除小鼠中首次观察到自发性自身免疫性疾病以来，人们推测PD-1在自身免疫调节中发挥着重要作用，但具体机制尚不清楚。最近的研究清楚地表明，PD-1在免疫耐受中具有双重作用：诱导和维持外周耐受。抗原呈递细胞上的PD-1配体（PD-Ls）已被证明可使自身反应性T细胞失活并诱导外周耐受，而实质细胞上的PD-Ls则通过抑制效应T细胞来防止组织破坏以维持耐受。此外，PD-1和其他免疫抑制受体已被证明在耐受调节中相互协作。在此，我们综述了关于PD-1在免疫耐受中作用的最新研究，并讨论了PD-1调控的可能临床应用。
