Departments of Neurology and Immunobiology, Yale School of Medicine, New Haven, CT 06511, USA.
Montreal Neurologic Institute, Montreal, Quebec, Canada.
Sci Immunol. 2020 Sep 18;5(51). doi: 10.1126/sciimmunol.abb8786.
T cells provide critical immune surveillance to the central nervous system (CNS), and the cerebrospinal fluid (CSF) is thought to be a main route for their entry. Further characterization of the state of T cells in the CSF in healthy individuals is important for understanding how T cells provide protective immune surveillance without damaging the delicate environment of the CNS and providing tissue-specific context for understanding immune dysfunction in neuroinflammatory disease. Here, we have profiled T cells in the CSF of healthy human donors and have identified signatures related to cytotoxic capacity and tissue adaptation that are further exemplified in clonally expanded CSF T cells. By comparing profiles of clonally expanded T cells obtained from the CSF of patients with multiple sclerosis (MS) and healthy donors, we report that clonally expanded T cells from the CSF of patients with MS have heightened expression of genes related to T cell activation and cytotoxicity.
T 细胞为中枢神经系统(CNS)提供重要的免疫监视,脑脊液(CSF)被认为是它们进入的主要途径。进一步描述健康个体 CSF 中 T 细胞的状态对于理解 T 细胞如何在不损害 CNS 脆弱环境的情况下提供保护性免疫监视以及为理解神经炎症性疾病中的免疫功能障碍提供组织特异性背景非常重要。在这里,我们对健康供体的 CSF 中的 T 细胞进行了分析,并确定了与细胞毒性能力和组织适应性相关的特征,这些特征在克隆扩增的 CSF T 细胞中得到了进一步例证。通过比较从多发性硬化症(MS)患者和健康供体的 CSF 中获得的克隆扩增 T 细胞的特征,我们报告说,来自 MS 患者 CSF 的克隆扩增 T 细胞表达与 T 细胞激活和细胞毒性相关的基因水平升高。