Resident memory T Cell heterogeneity in the human brain 4210

Abstract Description Resident memory T cells (TRM) populate various tissues, including the central nervous system (CNS), where they provide rapid, site-specific responses to secondary challenges. Mouse studies show that CNS T cells are vital for protection against neurotropic pathogens, play roles in neurological disorders, and contribute to normal CNS homeostasis. However, little is known about human brain TRM due to challenges in tissue collection. In this study, we utilized a unique method for obtaining tissues via on-site autopsies and rapid dissociation methods, acquiring samples from multiple sites in the CNS and peripheral tissues like lung and skin. Using high-parameter flow cytometry, we identified similar frequencies of TRM, marked by CD69+ CD103+, in both CNS and peripheral tissues. Single-cell RNA sequencing revealed that parenchymal T cells clustered together, characterized by CD69 and Hobit, while meningeal T cells formed a distinct cluster with a significant population of activated TRM-like cells expressing Granzyme B and IFNg. Similar TRM activation patterns and inflammatory states were found in brain tissue from epilepsy surgeries. Additionally, barcoded tetramers identified Flu and COVID-specific T cells in the brain without active infection, indicating virus-specific TRM can persist in the CNS. These results highlight the diverse populations of TRM in human CNS tissues and their potential implications in various diseases, including autoimmunity, neurodegeneration and infection. Funding Sources Supported by NIA R01AG078761 Topic Categories Neuroimmunology (NEUR)