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

组织驻留T淋巴细胞是组织限制性免疫的主要参与者。它们被认为在再次感染期间或针对与以前遇到的病原体相似的病原体提供关键水平的保护。虽然驻留T细胞的表型和组织分布已经很好地确定了，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。这关系到它们的动态、稳定性和转折性，也关系到它们在继发感染中提供的保护类型和质量。事实上，免疫保护的哪些方面仍然很不清楚：仅由常驻细胞执行，由常驻细胞和非常驻细胞相互提供，还是仅由进入感染组织的循环细胞提供。到目前为止，由于缺乏实用的工具来绘制体内驻留T细胞的命运图并进行追踪，这种描述受到了限制。到目前为止，我们也缺乏有选择地安装驻留但同时循环病原体特定的记忆细胞被移除的方法。这样的设置是评估常驻牢房保护能力的先决条件。为了绕过这些先前的限制，我们开发了两个新的转基因小鼠模型，以促进这类研究。在这些小鼠的帮助下，我们现在可以解决上述问题，我们可以用一种高度特异的方法来探索几个候选分子如何影响常驻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.