We used transgenic expression of capsid antigens (coat antigens VP1 & VP2) to Theiler’s murine encephalomyelitis virus (TMEV) to study how the immune response to VP1 and VP2 influences spinal cord demyelination, remyelination and axonal loss during the acute and chronic phases of infection. Expression from birth of capsid antigen resulted in immune tolerance to the antigen and absence of an immune response to the respective capsid antigen following virus infection. The transgenic mice featured more remyelination at all three chronic time points (90, 180 and 270 dpi) than transgene-negative controls. Interestingly, at 270 dpi, remyelination in VP1+ mice tended to be higher and more complete than that in VP2+ mice. Compared with transgene- negative controls, VP1+ and VP2+ animals showed similar demyelination in but less only late in the disease (270 dpi). The number of mid-thoracic axons at the last time point correlated with the levels of remyelination. The reduced loss of axons in VP1+ mice with remyelination was driven by counts in medium- and large-calibre axons. This study supports the hypothesis that expression of viral capsid proteins as self and subsequent genetic deletion of capsid-specific T cells influences the extent of spinal cord remyelination following Theiler’s virus-induced demyelination. We propose that VP1- and, to a lesser extent, VP2-specific CD8+ T cells limit and/or prevent the naturally occurring process of remyelination. This finding may have relevance to human multiple sclerosis, as targeted removal of CD8+ T cells specific for a yet-to-be-discovered causative peptide may enhance remyelination and prevent axonal loss in patients.
Denic A, Wootla B, Zoecklein L, Rodriguez M.Deletion of Virus-specific T-cells Enhances Remyelination in a Model of Multiple Sclerosis. J Neurol Transl Neurosci. 2014;2(1). pii: 1032.
TMEV is a natural infection of mice and causes oligodendrocyte damage thought to be due to CD4-mediated autoimmunity. In this study they render the immune system tolerant so that it will not contribute to viral cell removal and in this case they get more repair. Is this because the infected oligodendrocytes are not killed but they suggest that removal of CD8 cells could enhance remyelination, which in turns limits nerve loss. The treatment that depletes CD8 T cells is Alemtuzumab. Is this part of the mechanism why some people get an improved EDSS after Lemtrada treatment. Another explanation is that getting rid of thepathogenic response allows the natural repair processes to do their job.