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

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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.