Development and functions of tissue resident memory T cells during EAE

项目摘要 多发性硬化症(MS)是一种以中枢神经系统(CNS)为特征的自身免疫性疾病 由脱髓鞘、轴突丧失和进行性残疾引起。这种疾病可以在复发、缓解或更多的情况下发生 慢性病程。同样，实验性自身免疫性脑脊髓炎(EAE)模型的特点是中枢神经系统 炎症和脱髓鞘，每一种都概括了MS的某些方面，尽管有丰富的 关于不同循环T辅助细胞(Th)亚群与多发性硬化症(MS)的关联的知识， 关于组织驻留记忆T细胞的特征和功能的信息很少 (TRM)是最近在中枢神经系统(CNS)和脑脊液中发现的 多发性硬化患者的脑脊液。为了解决这一差距，我们使用了一种新开发的小鼠品系来鉴定， 追踪、鉴定和消除实验性自身免疫性脑脊髓炎(EAE)过程中的TRMS。 我们认为，自身反应性CNS CD4TRM表达一组独特的标记物，将它们与其他 循环中枢记忆T细胞在疾病进展中起着重要作用。使用我们最新开发的 工具，我们将表征在EAE期间CD4TRM细胞的分布、动力学和特征，建立 在EAE期间，它们是否再循环并参与疾病的进展和复发。这项工程的完成 该提案将帮助我们了解记忆T细胞如何促进慢性自身免疫，并可能导致 开发治疗多发性硬化症的新疗法

Project Summary Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by demyelination, axonal loss, and progressive disability. The disease can follow a relapsing remitting or a more chronic course. Similarly, experimental autoimmune encephalomyelitis (EAE) models are characterized by CNS inflammation and demyelination, and each recapitulate some aspects of MS. Although there is a wealth of knowledge regarding the association of different circulating T helper (Th) subsets with multiple sclerosis (MS), there is a paucity of information regarding the characteristics and functions of tissue resident memory T cells (TRM) which have been recently identified in the central nervous system (CNS) and the cerebrospinal fluid (CSF) of MS patients. To begin to address this gap, we have used a newly developed mouse strain to identify, track, characterize and eliminate TRMs during the course of experimental autoimmune encephalomyelitis (EAE). We propose that autoreactive CNS CD4+ TRM express a unique set of markers that distinguish them from other circulating central memory T cells and play an important role in disease progression. Using our newly developed tools, we will characterize the distribution, kinetic and characteristics of CD4+ TRM cells during EAE, establish whether they recirculate and participate in disease progression and relapses during EAE. The completion of this proposal will help us understand how memory T cells promote chronic autoimmunity and may lead to the development of novel therapies for MS.