Transcriptomic and clonal characterization of T cells in the human central nervous system
Jenna L. Pappalardo, Le Zhang, Maggie Pecsok, Kelly Perlman, Chrysoula Zografou, Khadir Raddassi, Ahmad Abulaban, Smita Krishnaswamy, Jack P. Antel, David van Dijk, David A. Hafler
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.