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Transcriptomic and clonal characterization of T cells in the human central nervous system

Snapshot of the cerebrospinal fluid

The central nervous system (CNS) is equipped with mechanisms to protect against unwanted inflammation, while still allowing immune surveillance for pathogens. Pappalardo et al. T cells profiled in the cerebrospinal fluid (CSF) of healthy individuals and multiple sclerosis (MS) patients using single cell RNA and TCR sequences to define CNS immune homeostasis in both healthy subjects and MS patients. In healthy individuals, clonally expanded CSF T cells are widely distinct from those found in blood with effector, IFNg, and tissue adaptation signatures, while CSF T cells from MS patients differ from healthy controls with a consistent gene expression signature with high activation and cytotoxicity. These results provide insight into the unique immune environment in CSF under normal and disease-associated conditions.


T cells provide critical immune surveillance of the central nervous system (CNS) and cerebrospinal fluid (CSF) is believed to be the primary route of their entry. Further characterization of T cell status in cerebrospinal fluid in healthy individuals is important to understand how T cells provide protective immune surveillance without harming the delicate CNS environment and providing a tissue-specific context for understanding immune dysfunction in neuroinflammatory disease. . Here, we profiled T cells in CSF from healthy human donors and identified signatures related to cytotoxic capacity and tissue adaptation that are further exemplified in clonally expanded CSF T cells. By comparing the profiles of clonally expanded T cells obtained from CSF of multiple sclerosis (MS) patients and healthy donors, we report that clonally expanded T cells from CSF of MS patients have increased expression of genes related to T cell activation and to cytotoxicity.

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