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

项目1：肾移植中巨细胞病毒感染期间异种免疫的系统分析 总结/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性疱疹病毒 感染，主要的球员是巨细胞病毒（CMV）。原发性感染和潜伏期通常 在免疫活性宿主中无症状发生。在免疫功能低下的患者中，CMV与 宿主是一种不稳定的平衡，可导致病毒再活化，这是一种与高发病率相关的现象 and mortality.该项目的总体目标是确定CMV感染对先天性和适应性的影响。 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，在免疫前、免疫过程中识别先天性和适应性免疫表型的连续体， 和CMV感染后将提供对CMV发病机制的机制见解和新的工具来选择， 监测和完善临床实践，从而改善患者的治疗效果。我们还假设接触CMV 在免疫功能低下的移植受者中初次感染或再活化后， 供体抗原，从而增加同种异体移植排斥反应的风险。更好地理解了 CMV和同种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。构建纵深纵向免疫 CMV感染期间肾移植受者的特征。我们假设CMV感染/再激活是 与共同的免疫特征相关，提供了一个机制框架，以确定风险的生物标志物 评估和指导治疗。目标2.确定CMV感染对异源性 T细胞同种免疫我们假设，CMV和同种异体抗原特异性T细胞的TCR交叉反应性将导致CMV感染。 促进异源免疫，导致同种免疫增加和抗病毒应答增强。

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.