Predicting Lung Allograft Rejection Using CMV-Specific T-cell Responses

描述（由申请人提供）：巨细胞病毒（CMV）是疱疹病毒科的一种DNA病毒。初次感染后，巨细胞病毒变得潜伏，并有可能在未来重新激活潜伏病毒。巨细胞病毒（CMV）是肺移植后最重要的致病源，可引起有害的直接影响（肺炎）和间接影响，如增强供体肺（同种异体移植物）的排斥反应。肺移植患者长期生存的限制因素是同种异体移植排斥反应。多项研究证实巨细胞病毒感染与排斥反应之间存在密切关联。CMV特异性T细胞反应在控制CMV复制中非常重要，但很少有研究评估CMV特异性T细胞介导的免疫在排斥反应中的作用，特别是对肺同种异体移植物。本研究的中心目标是确定肺移植患者CMV特异性T细胞反应的测量是否可以作为异体移植排斥反应风险和CMV负荷控制不良的预测因子。本研究的目的是：1。确定循环cmv特异性t细胞反应是否预测移植受者对肺同种异体移植排斥反应的保护作用。2. 确定肺移植排斥反应与亚临床巨细胞病毒感染在血液和肺部的关系。3. 确定巨细胞病毒特异性t细胞反应在肺中的作用，以预测肺同种异体移植排斥反应和肺病毒载量降低的保护作用。CMV特异性t细胞反应和病毒载量的研究结果可能有助于改进当前的抗病毒策略，并将为CMV复制与同种异体移植排斥之间的关系提供新的知识。开展这项研究并完成职业发展活动将使该候选人能够很好地建立独立的临床研究事业，专注于将病毒发病机制和抗病毒免疫的新发现应用于免疫功能低下和健康的病毒感染儿童。相关性（见说明书）：巨细胞病毒（CMV）是一种普遍存在的病毒感染，在健康人群中无症状，但在免疫功能低下的患者(如新生儿（先天性巨细胞病毒）和移植受者中引起重大疾病。从这个建议中增加的关于肺移植患者对巨细胞病毒的t细胞免疫的知识可能适用于其他人群（如新生儿），并可能对巨细胞病毒疫苗的开发有用。（摘要结束）

DESCRIPTION (provided by applicant): Cytomegaloviurs (CMV) is a DNA virus in the family Herpesviridae. After primary infection, CMV becomes latent with potential for future reactivation ofthe latent virus. Cytomegalovirus (CMV) is the most important source of morbidity from an infectious pathogen following lung transplantation, causing deleterious direct effects (pneumonia) and indirect effects, such as enhanced rejection of the donor lung (allograft). The limiting factor in the long-term survival of lung transplantation patients is allograft rejection. Multiple studies have confirmed a strong association between CMV infection and rejection. CMV-specific T-cell responses are very important in controlling CMV replication, but very little investigation has been done in evaluating the role of CMV-specific T cell-mediated immunity in the context of rejection, particularly for lung allografts. The central objective of this proposal is to determine if the measurement of CMV-specific T cell responses in lung transplant patients can be used as a predictor of the risk of allograft rejection and poor control of CMV load. The aims of the study are: 1. Determine if circulating CMV-specific T-cell responses predict protection from lung allograft rejection in transplant recipients. 2. Determine the relationship of lung allograft rejection with subclinical CMV infection in the blood and lung. 3. Determine the role of CMV-specific T-cell responses in the lung for predicting protection from lung allograft rejection and decreased lung viral load. Results from the proposed studies of CMV-specific T-cell responses and viral load may allow improvement of current anti-viral strategies, and will provide new knowledge about the relationship between CMV replication and allograft rejection. Conducting this study and completing the career development activities will allow this candidate to be well-positioned to establish an independent clinical research career focusing on application of new discoveries in viral pathogenesis and anti-viral immunity to the benefit of immunocompromised and healthy children with viral infections. RELEVANCE (See instructions): Cytomegalovirus (CMV) is a ubiquitous viral infection, which is asymptomatic in healthy people but causes significant disease in immunocompromised patients, such as neonates (congenital CMV) and transplant recipients. Increased knowledge from this proposal about T-cell immunity to CMV in a lung transplant patient may be applicable to other populations (e.g. neonate) and may be useful for CMV vaccine development. (End of Abstract)