Adaptive immune responses of γδ T cells in murine cytomegalovirus infections

人巨细胞病毒（HCMV）是导致免疫功能低下患者发病和新生儿围产期病理学的主要病毒原因。没有CMV特异性疫苗可用，抗病毒化疗导致相当大的副作用，并经常诱导耐药性。我们先前发表的在感染小鼠CMV（MCMV）的小鼠中的发现提供了明确的证据，即γδ T细胞控制急性CMV感染，特别是当常规适应性免疫机制不足时。γδ T细胞应答的几个特征显示了适应性免疫应答的特征。最近，在异基因干细胞移植后的患者中，还显示了响应于HCMV再活化的γδ T细胞的适应性扩增。这些发现表明人类和小鼠中γδ T细胞对巨细胞病毒的病毒免疫监视机制相似，并鼓励开发新的治疗概念。因此，我们希望使用MCMV感染模型来回答有关γδ T细胞在适应性免疫应答中的生物学的重要问题。为此目的，我们首次建立了一种转基因小鼠模型，其中将确定的TCRδ链插入TCRδ基因座。从针对MCMV的免疫应答中分离插入的TCRδ链。本研究拟利用这种δTCR转基因小鼠研究MCMV感染后γδ T细胞的迁移、增殖、效应功能及记忆的建立。该项目是研究组FOR2799“通过γδ T细胞受体接收和翻译信号”申请的一部分，该项目将受益于与申请中指定的FOR2799内其他组的相互作用。

The human cytomegalovirus (HCMV) is the leading viral cause of morbidity in immune compromised patients and perinatal pathology in newborns. There are no CMV specific vaccines available and antiviral chemotherapy results in considerable side effects and frequently induces drug resistance. Our previous published findings in mice infected with mouse CMV (MCMV) provide clear evidence that γδ T cells control acute CMV infections, particularly when conventional adaptive immune mechanisms are insufficient. Several characteristics of the γδ T cell response showed features of adaptive immune responses. Recently, in patients after allogeneic stem cell transplantation adaptive expansions of γδ T cells in response to HCMV reactivation have also been shown. These findings suggest similar mechanisms of viral immune surveillance to cytomegalovirus by γδ T cells in humans and in mice and encourage the development of new therapeutic concepts. We therefore want to use the MCMV infection model to answer important questions regarding the biology of γδ T cells in adaptive-like immune responses. For this purpose, we created for the first time a transgenic mouse model in which a defined TCRδ chain is inserted into the TCRδ locus. The inserted TCRδ chain was isolated from the immune response against MCMV. With the help of such a δTCR transgenic mice we will to study migration, proliferation, effector functions and establishment of memory of γδ T cells during MCMV infection. This project is part of the application for a Research Group FOR2799 “Receiving and Translating Signals via the γδ T Cell Receptor” and the project will benefit from the interactions with the other groups within the FOR2799 which are specified in the application.