Untersuchung des Einflusses von regulatorischen T Zellen auf die Immunantwort gegen eine Maus-Cytomegalovirus-Infektion

巨细胞病毒是广泛存在的重要病原体，以复杂的方式与宿主相互作用。它们编码大量的免疫调节基因，特异性地干扰免疫反应的不同过程。最近，有研究表明巨细胞病毒感染树突状细胞，而树突状细胞负责引发适应性免疫反应，使其无法执行该功能。我们已经能够鉴定出特异性下调共刺激分子CD86细胞表面表达的病毒基因，即基因modB7-2 （Loewendorf et al., 2004）。在这方面，缺乏共刺激分子的DC参与调节性T细胞的产生是很重要的。这些细胞已被证明通过限制效应T细胞对人类巨细胞病毒（HCMV）、单纯疱疹病毒（HSV）和其他病原体的反应，与免疫反应的平衡有关。概述项目的目的是鉴定调节性T细胞并表征其在MCMV感染期间的体内作用。此外，它着手评估DC调节对诱导调节性T细胞的重要性，以及免疫调节基因modB7-2在此背景下的具体作用。由此获得的数据将为高度适应性病原体与免疫系统相互作用的一个尚未调查的方面提供第一个见解。

Cytomegaloviruses are widespread, important pathogens that interact with their hosts in a complex fashion. They encode a large number of immunomodulatory genes interfering specifically with different processes of the immune response. Recently, it has been shown that cytomegaloviruses infect dendritic cells which are responsible for the elicitation of an adaptive immune response, rendering them unable to perform that function. We have been able to identify the viral gene that specifically downmodulates the cell surface expression of the costimulatory molecule CD86, the gene modB7-2 (Loewendorf et al., 2004). In this respect it is important that DC lacking costimulatory molecules are involved in the generation of regulatory T cells. These cells have been shown to be relevant for the balance of immune responses by restricting effector T cell responses against human cytomegalovirus (HCMV), herpes simplex virus (HSV) and other pathogens. The aim of the outlined project is the identification of regulatory T cells and the characterization of their in vivo role during a MCMV infection. Furthermore, it sets out to assess the importance of the modulation of DC for the induction of regulatory T cells and the specific role of the immunomodulatory gene modB7-2 in this context. The thereby acquired data will provide a first insight into a yet uninvestigated aspect of the interaction of a highly adapted pathogen with the immune system.