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

描述（由申请方提供）：巨细胞病毒（CMV）是疱疹病毒科的一种DNA病毒。初次感染后，CMV变为潜伏状态，并有可能在将来重新激活潜伏病毒。巨细胞病毒（CMV）是肺移植后感染性病原体的最重要的发病来源，引起有害的直接效应（肺炎）和间接效应，例如供体肺（同种异体移植物）的排斥反应增强。限制肺移植患者长期生存的因素是同种异体肺移植排斥反应。多项研究已经证实CMV感染和排斥反应之间有很强的相关性。CMV特异性T细胞反应在控制CMV复制中非常重要，但在评价CMV特异性T细胞介导的免疫在排斥反应中的作用方面，特别是在肺同种异体移植物中，研究很少。本提案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用作同种异体移植排斥反应和CMV负荷控制不良风险的预测因子。本研究的目的是：1.确定循环CMV特异性T细胞反应是否可预测移植受者的肺移植排斥反应。2.明确肺移植排斥反应与血液和肺亚临床CMV感染的关系。3.确定肺中CMV特异性T细胞反应在预测肺移植排斥反应和肺病毒载量降低中的作用。CMV特异性T细胞应答和病毒载量的拟议研究结果可能会改善目前的抗病毒策略，并将提供有关CMV复制和同种异体移植排斥反应之间关系的新知识。开展本研究并完成职业发展活动将使该候选人能够很好地建立一个独立的临床研究职业生涯，专注于应用病毒发病机制和抗病毒免疫的新发现，以造福免疫功能低下和健康的病毒感染儿童。相关性（参见说明）：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中引起重大疾病，如新生儿（先天性CMV）和移植受体。从这一提议中增加的关于肺移植患者对CMV的T细胞免疫的知识可能适用于其他人群（例如新生儿），并且可能对CMV疫苗开发有用。 (End摘要）

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)