Adaptive immune responses of γδ T cells in murine cytomegalovirus infections

鼠巨细胞病毒感染中γδT细胞的适应性免疫反应

• 批准号: 411763100
• 负责人: Professor Dr. Thomas Winkler
• 金额: --
• 依托单位: L f Genetik - AG Thomas Winkler
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/411763100?language=en
• 关键词: Adaptive; immune; responses; cells; murine

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.

人巨细胞病毒(HCMV)是免疫功能低下患者发病和新生儿围产期病理的主要病毒原因。目前还没有CMV特异性疫苗可用，抗病毒化疗会导致相当大的副作用，并经常导致耐药性。我们之前发表的在感染小鼠巨细胞病毒的小鼠身上的研究结果提供了明确的证据，表明γδT细胞控制急性巨细胞病毒感染，特别是当传统的适应性免疫机制不足时。γδT细胞反应的几个特征显示出适应性免疫反应的特征。最近，在异基因干细胞移植后的患者中，也显示了γδT细胞对巨细胞病毒重新激活的适应性扩增。这些发现表明，在人类和小鼠中，γδT细胞对巨细胞病毒的病毒免疫监测机制相似，并鼓励开发新的治疗概念。因此，我们希望使用巨细胞病毒感染模型来回答有关γδT细胞在适应性免疫反应中的生物学方面的重要问题。为此，我们首次建立了转基因小鼠模型，在该模型中，定义的TcRδ链被插入到TcRδ基因座。从抗巨细胞病毒的免疫应答中分离到插入的TCRδ链。借助该转基因小鼠，我们将研究δ感染过程中γδT细胞的迁移、增殖、效应功能和记忆的建立。该项目是研究小组FOR2799“通过γδT细胞受体接收和转换信号”申请的一部分，该项目将从与FOR2799中指定的其他小组的互动中受益。