La Rosa Corinna, Krishnan Aparna, Longmate Jeff, Martinez Joy, Manchanda Pooja, Lacey Simon F, Limaye Ajit P, Diamond Don J
Laboratory of Vaccine Research, Beckman Research Institute of the City of Hope, City of Hope Comprehensive Cancer Center, Duarte, California 91010, USA.
J Infect Dis. 2008 Jan 1;197(1):25-33. doi: 10.1086/523652.
Immunological parameters that distinguish solid-organ transplant (SOT) recipients at risk for life-threatening cytomegalovirus (CMV) disease are being actively pursued to aid posttransplant management. A candidate marker is programmed death (PD)-1 receptor, whose overexpression has been associated with disease progression during persistent viral infections. To determine whether levels of this negative regulator of T cell activity are altered in SOT recipients with symptoms of CMV disease, a comparative PD-1 expression analysis was done in healthy, CMV-positive individuals and in liver transplant recipients. PD-1 levels were measured among the total population of CD8(+) and CD8(+) T cells binding to CMV-specific major histocompatibility complex class I tetramers. Minimal PD-1 expression was found in the healthy, CMV-positive cohort, and symptomatic SOT recipients had significantly higher PD-1 levels. PD-1 up-regulation was significantly associated with incipient and overt CMV disease and with viremia. Our findings suggest that PD-1 could be developed as a prognostic tool to predict CMV disease and guide therapeutic interventions.
目前正在积极寻找能够区分有危及生命的巨细胞病毒（CMV）疾病风险的实体器官移植（SOT）受者的免疫参数，以辅助移植后的管理。一个候选标志物是程序性死亡（PD）-1受体，其过度表达与持续性病毒感染期间的疾病进展有关。为了确定在有CMV疾病症状的SOT受者中这种T细胞活性负调节因子的水平是否发生改变，我们在健康的CMV阳性个体和肝移植受者中进行了一项比较性的PD-1表达分析。在与CMV特异性主要组织相容性复合体I类四聚体结合的CD8(+)和CD8(+) T细胞的总群体中测量了PD-1水平。在健康的CMV阳性队列中发现PD-1表达最低，有症状的SOT受者的PD-1水平显著更高。PD-1上调与早期和明显的CMV疾病以及病毒血症显著相关。我们的研究结果表明，PD-1可以作为一种预测工具来预测CMV疾病并指导治疗干预。
