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

Autor: Pappalardo, Jenna L., Zhang, Le, Pecsok, Maggie K., Perlman, Kelly, Zografou, Chrysoula, Raddassi, Khadir, Abulaban, Ahmad, Krishnaswamy, Smita, Antel, Jack, van Dijk, David, Hafler, David A.
Zdroj: Science Immunology; 2020, Vol. 5 Issue 51, p1-14, 14p
Abstrakt: 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. 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index