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Cerebrospinal fluid snapshot
The central nervous system (CNS) features mechanisms to protect against untoward inflammation yet allowing immune surveillance for pathogens. Pappalardo et al. profiled T cells in the cerebrospinal fluid (CSF) of healthy individuals and patients with multiple sclerosis (MS) using single-cell RNA and TCR sequences to define CNS immune homeostasis in both healthy donors and patients with MS. In healthy individuals, clonally expanded CSF T cells are largely distinct from those found in the blood with effector, IFNγ, and tissue adaptation signatures, whereas CSF T cells from patients with MS differ from healthy controls with a gene expression signature consistent with elevated activation and cytotoxicity. These findings provide insight into the unique immune environment in the CSF under normal and disease-associated conditions.
Abstract
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.
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