Can studying the pathology of MS and animal models of MS teach us about the cell types driving MS?
Professor Lassmann is the doyen of multiple sclerosis pathology. He makes two very important points in this review.
- EAE the experimental model of MS is not MS. Interestingly, most EAE models are driven by CD4+ T-cells, which is very relevant to the second point he makes. Does this mean we should not be using EAE to make decisions about the cause and pathogenesis of MS?
- He states that MS is mediated by B-cells and CD8+ T-cells and not CD4+ T-cells. This is quite a profound comment, which is backed up by his observations studying literally thousands of MS biopsies and post-mortem cases. The question which his observation raises is what are the CD8+-T cells doing? Is it the regulatory CD8+ cells or is or the cytotoxic CD8+ cells? In relation to his B-cell statement, we have already made the case for it being the memory B-cell.
Lassmann Hans. The changing concepts in the neuropathology of acquired demyelinating central nervous system disorders. Curr Opin Neurol. 2019 Mar 19.
PURPOSE OF REVIEW: Research on multiple sclerosis (MS) pathogenesis and therapy is to a large extent driven by results obtained in experimental autoimmune encephalomyelitis (EAE). This approach provided deep insights into the mechanism of brain inflammation and immune-mediated tissue injury and, thus, most of our currently established therapies for MS patients have been developed with profound contributions of experimental autoimmune research. Recent data, which are summarized in this review article, however, show important differences between EAE and MS.
RECENT FINDINGS: EAE models perfectly reproduce a disease, now called myelin oligodendrocyte glycoprotein (MOG) antibody-associated inflammatory demyelinating disease, which, however, is different from classical MS. In MS, the inflammatory reaction in the brain is dominated by CD8 T-lymphocyte and CD20 B cells. Demyelination in MS appears to be triggered by soluble factors, produced by T cells and/or B cells, which are different from anti-MOG antibodies seen in EAE, and induce widespread MS like primary demyelination and tissue damage associated with oxidative injury, mitochondrial damage and subsequent ‘virtual’ hypoxia.
SUMMARY: To define the antigenic target of the inflammatory reaction, the nature of the inflammatory response and the mechanisms of tissue injury are key topics of ongoing MS research.