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: 7708390
• 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/7708390
• 关键词: Allografting; 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-Lymphocyte; Testing; Time; Transplant Recipients; Transplantation; Viral; Viral Load result; Viral Pathogenesis; Virus; Virus Diseases; Work; abstracting; 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; response; time interval; time use; vaccine development

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)

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，CMV 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) 是肺移植后感染性病原体最重要的发病来源，可引起有害的直接影响（肺炎）和间接影响，例如增强供体肺（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。多项研究已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 细胞反应对于控制 CMV 复制非常重要，但在评估 CMV 特异性 T 细胞介导的免疫在排斥反应中的作用方面进行的研究很少，特别是对于肺同种异体移植物。该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以用作同种异体移植排斥风险和 CMV 负荷控制不良的预测因子。该研究的目的是： 1. 确定循环 CMV 特异性 T 细胞反应是否可以预测移植受者免受肺同种异体移植排斥反应的保护。 2.确定肺同种异体移植排斥与血液和肺部亚临床CMV感染的关系。 3. 确定肺中 CMV 特异性 T 细胞反应的作用，以预测肺同种异体移植排斥和肺病毒载量降低的保护作用。拟议的 CMV 特异性 T 细胞反应和病毒载量研究结果可能有助于改进当前的抗病毒策略，并将提供有关 CMV 复制与同种异体移植排斥之间关系的新知识。进行这项研究并完成职业发展活动将使该候选人能够处于有利地位，建立独立的临床研究职业，重点关注病毒发病机制和抗病毒免疫方面的新发现的应用，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，在健康人中无症状，但在免疫功能低下的患者中引起严重疾病，例如新生儿（先天性 CMV）和移植受者。从该提案中获得的有关肺移植患者 T 细胞对 CMV 免疫的更多知识可能适用于其他人群（例如新生儿），并且可能有助于 CMV 疫苗的开发。 （摘要完）