Neurology and Neurosurgery

Oct. 27, 2023

The pathogenic mechanisms driving disease progression in multiple sclerosis (MS) haven't been elucidated. A Mayo Clinic study provides evidence that neuroantigen-specific T cells infiltrate demyelinated portions of the central nervous system, promoting neuron loss and disease progression.

The researchers used laboratory models of MS to investigate the pathogenesis of MS progression. The study will be published in the Journal of Clinical Investigation.

Key findings:

• Demyelination resulted in the presentation of a neuron-specific neoantigen to antigen-specific CD8+ T cells.
• In the setting of demyelination, CD8+ T cells proliferated and damaged neurons and axons.
• In the absence of demyelination, the neuroantigen-specific effectors surveilled the central nervous system but weren't retained.

The researchers also reported elevated neuronal expression of MHC class 1 transcripts and protein in gray matter and white matter tracts in post-mortem tissue from individuals with MS. Those findings support a pathogenic role for autoreactive anti-axonal and anti-neuronal CD8+ T cells in MS progression.

The researchers note that the findings have important implications for developing therapeutic strategies to prevent MS disease progression.

For more information

Clarkson BDS, et al. CD8+ T cells recognizing a neuron-restricted antigen injure axons in a model of multiple sclerosis. Journal of Clinical Investigation. In press.

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