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 and patients with MS. In healthy individuals, clonally expanded CSF T cells are largely distinct from those found in the blood with effector, IFNg, 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.
Transcriptomic and clonal characterization of T cells in the human central nervous system.Pappalardo JL, Zhang L, Pecsok MK, Perlman K, Zografou C, Raddassi K, Abulaban A, Krishnaswamy S, Antel J, van Dijk D, Hafler DA.Sci Immunol. 2020 Sep 18;5(51):eabb8786. doi: 10.1126/sciimmunol.abb878
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.
What are they killing…oligodendrocytes, nerves or virus?