Plasticity and effector function of tissue resident immune cells following pathogen challenge

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Tissue-resident T lymphocytes are major players in tissue-confined immunity. They are consid-ered to provide a critical level of protection during re-infections or against pathogens that are similar to a previously encountered pathogen. While the phenotype and the tissue distribution of resident T cells are well established, we still have a very limited understanding how these T cells respond when re-encountering a pathogen. This concerns their dynamics, stability, and turno-ver, but also the type and quality of protection they provide in secondary infections. In fact, it remains largely unclear which aspects of immune protection are: solely carried out by resident cells, mutually provided by resident and non-resident cells, or exclusively provided by circulating cells that enter infected tissues. Such characterizations were so far restricted by the absence of practical tools for in vivo fate-mapping and tracing of resident T cells. We so far also lacked ap-proaches to selectively install only resident but while circulating pathogen-specific memory cells are removed. Such a setups are prerequisites for assessing the protective capacity of resident cells. To bypass these prior limitations, we have developed two new transgenic mouse models that facilitate such studies. With the help of these mice we can now address the aforementioned questions and we can in a highly specific approach explore how several candidate molecules impact resident T cell function.