Checkpoint Blockade Optic Neuritis Is Characterized by CD8+ T Cells with Persistent Antigen Specificity

Despite its clinical significance, the pathogenic mechanisms driving this condition remain poorly understood, hampering the development of targeted therapies. Our study addresses this critical knowledge gap through an integrated multi-omics investigation of paired peripheral blood and cerebro-spinal fluid from well-characterized CBON cohorts.  We identify a previously unrecognized CD30+CD8+ T-cell population as the pathological hallmark of CBON.

These cells exhibit a stable cytotoxic-Th17 phenotype characterized by CD137, PD-1, IL-17A, and GZMB expression, persist longitudinally throughout the disease course, and show strong correlation with clinical severity metrics including visual acuity loss and radiological progression. A key advance of our work is the discovery that these CD30+CD8+ T cells demonstrate persistent reactivity against dominant epitopes of MOG and AQP4, mediated by a conserved TRAV20_TRBV28 TCR clonotype that is shared across patients and maintained over time.  Beyond mechanistic insights, our study provides important clinical-translational validation.