Identification of SARS-CoV-2-specific cytotoxic lymphocytes in cerebrospinal fluid of a patient with cerebral demyelination Post mRNA vaccination

Abstract

Some cerebral demyelinating lesions occur after vaccination. We aimed to elucidate the precise roles of vaccine-activated immune cells and antigen-specific lymphocytes in the central nervous system of a patient who developed cerebral demyelination after vaccination. Using comprehensive single-cell RNA sequencing and immune repertoire analysis combined with a lymphocyte stimulation assay, we characterized the immunological landscape of a patient who developed right-hand clumsiness after receiving an mRNA vaccine against SARS-CoV-2 and was subsequently diagnosed with tumefactive cerebral demyelination. Natural killer cells and effector CD8+ T cells in the cerebrospinal fluid were more cytotoxic and activated than those in healthy controls. Effector CD8+ T cells specific to SARS-CoV-2 spike peptides were identified in the cerebrospinal fluid. The proportion of these cells in peripheral blood decreased after corticosteroid therapy, in parallel with clinical improvement and a reduction in lesion size. Although a direct causal relationship between vaccination and demyelination remains uncertain, our findings suggest that vaccine-activated cytotoxic lymphocytes contribute to immune-mediated demyelinating events in the central nervous system.