Project 1: Systems Analyses of Heterologous Immunity During CMV Infection in Renal Transplantation

方案一：肾移植中巨细胞病毒感染时异种免疫的系统分析 摘要/摘要 实体器官移植的主要并发症是排斥反应和机会性潜伏疱疹病毒。 感染，主要是巨细胞病毒(CMV)。原发感染，以及潜伏期，通常 无症状地发生在免疫能力强的宿主中。在免疫低下的患者中，巨细胞病毒与 宿主是一种不稳定的平衡，可能导致病毒重新激活，这是一种与高发病率相关的现象 和死亡率。该项目的首要目标是确定CMV感染对先天和适应性的影响。 研究人员将研究移植受者的免疫反应，并将我们的发现传播给更广泛的科学界。 我们的中心假设是，在确定先天免疫和获得性免疫表型的连续体之前， 而CMV感染后将为CMV的发病机理提供机制上的洞察和新的选择工具， 监测和改进临床实践，从而改善患者的预后。我们还假设，接触CMV 免疫功能低下的移植受者在初次感染或重新激活时会引起交叉反应 供者抗原，因此增加了同种异体移植排斥反应的风险。提高对两国关系的理解 巨细胞病毒和同种异体免疫将为临床免疫评估和改进治疗提供实用工具。我们 计划通过以下目标实现这些目标：目标1.构建深度纵向免疫 肾移植受者巨细胞病毒感染情况分析。我们假设CMV感染/重新激活是 与提供用于识别风险生物标记物的机械框架的公共免疫简档相关联 评估和指导治疗。目的2.明确CMV感染在异源病毒产生中的作用 T细胞同种免疫。我们假设针对CMV和同种异体抗原的T细胞的TCR交叉反应将 促进异种免疫，增强同种免疫，增强抗病毒反应。

PROJECT 1: Systems Analyses of Heterologous Immunity During CMV Infection in Renal Transplantation SUMMARY/ABSTRACT The main complications of solid organ transplantations are rejection and opportunistic latent herpes virus infections, the predominant player being cytomegalovirus (CMV). Primary infections, as well as latency, normally occur asymptomatically in immunocompetent hosts. In immunocompromised patients, coexistence of CMV with the host is a precarious balance that can result in viral reactivation, a phenomenon associated with high morbidity and mortality. The overarching goal of the project is to define the effects of CMV infection on innate and adaptive immune responses in transplant recipients and to disseminate our findings to the broader scientific community. Our central hypothesis is that identifying the continuum of innate and adaptive immune phenotypes before, during and after CMV infection will provide mechanistic insights into CMV pathogenesis and novel tools to select, monitor and refine clinical practice, thereby improving patient outcomes. We also postulate that exposure to CMV upon primary infection or reactivation in immunocompromised transplant recipients induces crossreactivity to donor antigens, thus increasing the risk of allograft rejection. Improved understanding of the relationship between CMV and alloimmunity will provide practical tools for clinical immune assessment and improved therapies. We plan to reach these goals through the following Aims: Aim 1. Construct an in-depth longitudinal immune profile of renal transplant recipients during CMV infection. We hypothesize that CMV infection/reactivation is associated with a common immune profile providing a mechanistic framework to identify biomarkers for risk assessment and guiding therapy. Aim 2. Define the role of CMV infection on the generation of heterologous T cell alloimmunity. We hypothesize that TCR cross-reactivity of T cells specific for CMV and alloantigen will promote heterologous immunity, leading to increased alloimmunity and potentiation of antiviral responses.