Tissue-resident memory T cells in the multiple sclerosis brain and their relationship to Epstein-Barr virus infected B cells

Presence of EBV infected B cells and EBV-specific CD8 T cells in the multiple sclerosis (MS) brain suggests a role for virus-driven immunopathology in brain inflammation. Tissue-resident memory (Trm) T cells differentiating in MS lesions could provide local protection against EBV reactivation. Using immunohistochemical techniques to analyse canonical tissue residency markers in postmortem brains from control and MS cases, we report that CD103 and/or CD69 are mainly expressed in a subset of CD8+ T cells that intermingle with and contact EBV infected B cells in the infiltrated MS white matter and meninges, including B-cell follicles. Some Trm-like cells were found to express granzyme B and PD-1, mainly in white matter lesions. In the MS brain, Trm cells could fail to constrain EBV infection while contributing to sustain inflammation.