Function, specificity and homing of gamma delta T cells in peripheral tissues

早在个体发生的早期，寡克隆γδ T细胞亚群就聚集在粘膜组织中，在那里它们仍然构成免疫系统的一个神秘成分。分析γδ T细胞的功能是很困难的，因为据我们所知，在小鼠和人类中唯一的γδ T细胞特异性标记是γδ TCR本身。此外，我们已经证明γδ TCR在活化的γδ T细胞中经常下调。γδ T细胞的鉴定依赖于针对其TCR的单克隆抗体。然而，TCR γδ与抗体的连接会干扰正常的细胞功能，并在体内消耗它们。为了探索γδ T细胞在体内的功能，我们建立了一个敲入报告小鼠模型，其中所有的γδ T细胞都被核绿色荧光标记。我们的目的是利用该模型监测体内粘膜组织中γδ T细胞的分布和动力学，并确定γδ T细胞的细胞相互作用伙伴。此外，我们的模型提供了从粘膜组织中分离纯度最高的naïve γδ T细胞并在体外表征其功能的独特机会。最后，我们将分析控制γδ T细胞归巢的分子机制，并研究在多大程度上功能性γδ T细胞群可以在成年生物的粘膜中再生。

Already early in ontogeny, oligoclonal γδ T cell subsets populate mucosal tissues where they still constitute an enigmatic component of the immune system. The analysis of γδ T cell function is difficult because, to our knowledge, the only γδ T cell specific marker in mice and humans is the γδ TCR itself. Furthermore, we have shown that the γδ TCR is often downregulated in activated γδ T cells. The identification of γδ T cells relies on monoclonal antibodies directed against their TCR. TCR γδ ligation with antibodies interferes, however, with normal cell function and depletes them in vivo. In order to explore the function of γδ T cells in vivo, we have generated a ‚knock-in’ reporter mouse model, in which all γδ T cells are genetically labeled with a nuclear green fluorescence. Our aim is to employ this model to monitor the distribution and dynamics of γδ T cells in mucosal tissues in vivo and to identify cellular interaction partners of γδ T cells. Furthermore, our model offers the unique opportunity to isolate naïve γδ T cells of highest purity from mucosal tissues and to characterize their functions in vitro. Finally, we will analyze the molecular mechanisms that govern γδ T cell homing and we will study to what extent functional γδ T cell populations can be regenerated in the mucosa of an adult organism.