Bryant-Hudson Katie M, Carr Daniel J J
Department of Ophthalmology, Dean McGee Eye Institute, The University of Oklahoma Health Sciences Center, Room 415, 608 Stanton L Young Boulevard, Oklahoma, OK 73104, USA.
Clin Dev Immunol. 2012;2012:924619. doi: 10.1155/2012/924619. Epub 2012 Feb 28.
The inhibitory receptor, Programmed Death 1 (PD-1), and its ligands (PD-L1/PD-L2) are thought to play a role in immune surveillance during chronic viral infection. The contribution of the receptor/ligand pair during an acute infection is less understood. To determine the role of PD-L1 and PD-L2 during acute ocular herpes simplex virus type 1 (HSV-1) infection, HSV-1-infected mice administered neutralizing antibody to PD-L1 or PD-L2 were assessed for viral burden and host cellular immune responses. Virus titers were elevated in cornea and trigeminal ganglia (TG) of anti-PD-L1-treated mice which corresponded with a reduced number of CD80-expressing dendritic cells, PD-L1⁺ dendritic cells, and HSV-1-specific CD8⁺ T cells within the draining (mandibular) lymph node (MLN). In contrast, anti-PD-L2 treatment had no effect on viral replication or changes in the MLN population. Notably, analysis of CD11c-enriched MLN cells from anti-PD-L1-treated mice revealed impaired functional capabilities. These studies indicate PD-L1-expressing dendritic cells are important for antiviral defense during acute HSV-1 infection.
抑制性受体程序性死亡蛋白1（PD-1）及其配体（PD-L1/PD-L2）被认为在慢性病毒感染期间的免疫监视中发挥作用。而对于该受体/配体对在急性感染中的作用，人们了解较少。为了确定PD-L1和PD-L2在急性眼部单纯疱疹病毒1型（HSV-1）感染中的作用，对给予PD-L1或PD-L2中和抗体的HSV-1感染小鼠的病毒载量和宿主细胞免疫反应进行了评估。抗PD-L1治疗的小鼠角膜和三叉神经节（TG）中的病毒滴度升高，这与引流（下颌）淋巴结（MLN）内表达CD80的树突状细胞、PD-L1⁺树突状细胞和HSV-1特异性CD8⁺T细胞数量减少相对应。相比之下，抗PD-L2治疗对病毒复制或MLN群体变化没有影响。值得注意的是，对抗PD-L1治疗小鼠的富含CD11c的MLN细胞分析显示其功能能力受损。这些研究表明，表达PD-L1的树突状细胞在急性HSV-1感染期间的抗病毒防御中很重要。
