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

组织常驻T淋巴细胞是组织局限性免疫的主要参与者。它们被认为在再次感染或对抗与以前遇到的病原体相似的病原体时提供关键水平的保护。虽然常驻T细胞的表型和组织分布已经很好地确定，但我们对这些T细胞在再次遇到病原体时如何反应的了解仍然非常有限。这涉及到它们的动态、稳定性和周转率，但也涉及到它们在继发性感染中提供的保护的类型和质量。事实上，目前还不清楚免疫保护的哪些方面是：完全由常驻细胞发挥作用，由常驻细胞和非常驻细胞共同发挥作用，还是完全由进入感染组织的循环细胞发挥作用。到目前为止，由于缺乏用于体内命运定位和追踪驻留T细胞的实用工具，这种表征受到了限制。到目前为止，我们还缺乏选择性地只安装常驻但同时移除循环病原体特异性记忆细胞的方法。这种设置是评估常驻细胞保护能力的先决条件。为了绕过这些先前的限制，我们开发了两种新的转基因小鼠模型，以促进此类研究。在这些小鼠的帮助下，我们现在可以解决上述问题，我们可以以高度特异性的方法探索几种候选分子如何影响驻留T细胞功能。

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.