A pro-inflammatory effector-memory T cell program links peripheral EBV priming to CNS autoimmunity

A new study has shed light on the connection between Epstein-Barr virus (EBV) and multiple sclerosis (MS). The research reveals that EBV-specific T cells in the peripheral nervous system (peripheral T cells) may contribute to CNS autoimmunity in a unique way.

The study generated an atlas of blood and cerebrospinal fluid (CSF) T cells from untreated MS patients and healthy controls. It was found that T cells carrying the GZMK effector-memory program in the blood were disproportionately present in the CSF of MS patients. These cells were also associated with EBV reactivity.

In the CSF, EBV-reactive GZMK CD8 T cells were seen to interact with B lineage cells. These activated CD8 T cells were found to promote atypical B cell and plasmablast formation. Additionally, the GZMK-enriched effector-memory cells induced the release of pro-inflammatory cytokines IL-6 and IL-8 from myeloid cells.

Based on these findings, the researchers propose a new model where EBV-specific CD8 T cells contribute to inflammation in the central nervous system through a non-canonical mechanism, involving the activation of B cells and myeloid cells. This suggests that EBV may play a significant role in the development of MS through a complex interaction of T cells, B cells, and myeloid cells.