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The presence of EBV infected B cells in postmortem multiple sclerosis (MS) brain tissue suggests immune evasion strategies. Using immunohistochemical techniques we analysed the expression of the immune checkpoint molecule PD-L1 and its receptor PD-1 in MS brains containing B cell-enriched perivascular infiltrates and meningeal follicles, a major EBV reservoir. PD-1 and PD-L1 immunoreactivities were restricted to CNS-infiltrating immune cells. PD-L1 was expressed on B cells, including EBV infected B cells, while PD-1 was expressed on many CD8+ T cells, including EBV-specific CD8+ T-cells, and fewer CD4+ T cells. PD-L1+ cells and EBV infected cells were in close contact with PD-1+ T cells. PD-L1 expressed by EBV infected B cells could favour local immune evasion leading to EBV persistence and immunopathology in the MS brain. [Display omitted] • Most EBV infected B cells in the MS brain express the immune checkpoint molecule PD-L1. • The PD-L1 receptor PD-1 is expressed on MS brain-infiltrating T cells. • CNS-infiltrating EBV-specific CD8 T cells also express PD-1. • PD-1+ T cells contact PD-L1+ and EBV infected cells in MS lesions and meninges. • The PD-1-PD-L1 pathway may limit EBV elimination and sustain inflammation in the MS brain. [ABSTRACT FROM AUTHOR]