Behavior and function of virus-specific tissue-resident memory T cells

记忆T细胞是幼稚的抗原特异性T细胞的后代，在最初的反应过程中被克隆扩增，一旦抗原被消除，它就会存活下来。它们被广泛地分为两个主要的亚群，称为中央记忆T细胞和效应记忆T细胞。中枢记忆T细胞定位于次级淋巴组织，具有较高的增殖能力，但效应功能有限，而效应记忆T细胞通过非淋巴组织迁移，迅速产生效应细胞因子，但增殖能力有限。近年来，在皮肤表皮、脑、肠上皮和呼吸道粘膜中发现了一种新型的记忆T细胞。这些T细胞不会离开休眠宿主体内的原始组织，因此被称为组织驻留记忆T细胞。它们可能是针对这些组织的病原体的第一道防线。我们最近在病毒免疫小鼠的唾液腺中发现了一组独特的抗原特异性记忆CD8 T细胞，它们具有抗病毒活性，可能被认为是组织驻留记忆T细胞。此外，这些T细胞表达上皮性黏附分子E-钙粘附素，促进了它们在该组织中的积累。在这个项目的第一部分，我们将研究这个令人着迷的细胞群体的组织积累、解剖定位和动态平衡调节的机制。有趣的是，我们已经观察到唾液腺中的记忆CD8 T细胞在上皮内的定位类似于肠粘膜中的淋巴细胞。在正在进行的实验中，我们进一步鉴定了病毒免疫小鼠胸腺中的一组病毒特异性CD8T细胞，这些细胞也表达组织驻留记忆T细胞的标志。在这个项目的第二部分，我们将查明这些胸腺记忆T细胞是否确实是组织驻留的，并能够发挥抗病毒活性。此外，我们将确定这种胸腺记忆T细胞的产生是否需要局部抗原，这些T细胞定位于胸腺髓质中的细胞团和皮质中的单个细胞。胸腺是众所周知的初级淋巴器官，用于产生幼稚的T细胞，因此，它也可能是组织驻留记忆T细胞的场所的想法非常有趣。

Memory T cells are the progeny of naive antigen-specific T cells that have been clonally expanded in the course of a primary response and that survived once the antigen has been eliminated. They have been broadly divided into two main subsets termed central and effector memory T cells. Central memory T cells localize in secondary lymphoid tissues, show high proliferative potential but limited effector function whereas effector memory T cells migrate through non-lymphoid peripheral tissues, produce rapidly effector cytokines but exhibit limited proliferation capacity. In the past few years, a new type of memory T cells has been identified in the skin epidermis, the brain, the intestinal epithelium and the respiratory mucosa. These T cells do not exit their home tissues in the resting host and have therefore been termed tissue-resident memory T cells. They may represent a first line of defense against pathogens that target these tissues.We recently discovered a unique population of antigen-specific memory CD8 T cells in the salivary glands of virus-immune mice that exhibit anti-viral activity and that might be considered as tissue-resident memory T cells. Furthermore, these T cells expressed the epithelial adhesion molecule E-cadherin which promoted their accumulation in this tissue. In the first part of this project, we will investigate the mechanisms of tissue accumulation, anatomical localization and homeostatic regulation of this fascinating cell population. Interestingly, we already observed that memory CD8 T cells in the salivary glands show an intraepithelial localization similar to lymphocytes in the gut mucosa. In ongoing experiments, we further identified a population of virus-specific CD8 T cells in the thymus of virus-immune mice that also express markers characteristic of tissue-resident memory T cells. In the second part of this project, we will find out whether these thymic memory T cells are indeed tissue-resident and able to exert anti-viral activity. In addition, we will determine whether local antigen is required for the generation of such thymic memory T cells that localize as cell clusters in the thymic medulla and as single cells in the cortex. The thymus is a well-known primary lymphoid organ for the generation of naïve T cells and thus, the notion that it may also serve as a site for tissue-resident memory T cells is very intriguing.