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

使用 CMV 特异性 T 细胞反应预测肺同种异体移植排斥

• 批准号: 8307842
• 负责人: SHARON FEI-HSIEN CHEN
• 金额: $ 13.08万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-11 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8307842
• 关键词: Animal Model; Antigen Presentation; Appearance; Biological Assay; Blood; Bronchoalveolar Lavage Fluid; Cellular Immunity; Child; Chronic; Clinical Research; Cytomegalovirus; DNA Viruses; Dendritic Cells; Development; Disease; Early Diagnosis; Family; Frequencies; Future; Goals; Herpesviridae; Human; Immune response; Immunity; Immunocompromised Host; Immunology; Infection; Inflammatory; Instruction; Investigation; Ischemia; Knowledge; Laboratories; Latent Virus; Lung; Lung Transplantation; Measurement; Mediating; Modeling; Morbidity - disease rate; Outcome; Patients; Peptides; Pneumonia; Polymerase Chain Reaction; Population; Positioning Attribute; Principal Investigator; Research Infrastructure; Research Proposals; Risk; Role; Severities; Source; Structure of parenchyma of lung; T cell response; T-Lymphocyte; Testing; Time; Transplant Recipients; Transplantation; Viral; Viral Load result; Viral Pathogenesis; Virus; Virus Diseases; Work; allograft rejection; career; career development; chemokine; cytokine; experience; graft failure; in vivo; lung allograft; monocyte; neonate; novel; pathogen; patient oriented research; peripheral blood; physiologic model; protein expression; time interval; time use; vaccine development

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 ofthe 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 ofthe risk of allograft rejection and poor control of CMV load. The aims ofthe 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 behween 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.

巨细胞病毒（CMV）是疱疹病毒科的一种DNA病毒。初次感染后，CMV变成 潜伏的，有可能在将来重新激活潜伏的病毒。巨细胞病毒（CMV）是最重要的 肺移植后感染性病原体的发病源，引起有害的直接 影响（肺炎）和间接影响，如增强排斥反应的供体肺（同种异体移植）。的 肺移植患者长期存活的限制因素是同种异体移植排斥。多项研究 已经证实巨细胞病毒感染和排斥反应之间有很强的关联。CMV特异性T细胞应答 在控制CMV复制中非常重要，但在评估CMV复制中所做的研究很少。 CMV特异性T细胞介导的免疫在排斥反应中的作用，特别是对于肺同种异体移植物。的 该建议的中心目标是确定肺中CMV特异性T细胞应答的测量是否 移植患者可以作为移植物排斥反应和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细胞反应是否预测了对 移植受者的肺移植排斥反应。2.确定肺移植排斥反应与 血液和肺部亚临床CMV感染。3.确定CMV特异性T细胞应答在 用于预测肺移植排斥反应的保护和肺病毒载量的降低。结果 建议的CMV特异性T细胞应答和病毒载量的研究可能会改善目前的抗病毒药物， 策略，并将提供新的知识之间的关系CMV复制和移植 排斥反应进行这项研究并完成职业发展活动将使该候选人能够 有能力建立一个独立的临床研究事业，专注于新的应用 在病毒发病机理和抗病毒免疫方面的发现， 病毒感染的儿童。 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，但可引起 免疫功能低下患者的重大疾病，如新生儿（先天性CMV）和移植 受惠人士从这个提议中增加了对肺移植患者中CMV的T细胞免疫的知识 可适用于其他人群（如新生儿），并可用于CMV疫苗开发。