Encephalomyelitis-associated antimyelin autoreactivity induced by streptococcal exotoxins

Objective: After implicating Streptococcus pyogenes as causing acute dissem inated encephalomyelitis (ADEM) in a child, we wanted to prove that in vivo activation of autoreactive T lymphocytes by superantigens of this Streptoc occus contributed to the dramatic demyelination. Background: ADEM is a demy elinating disorder of the CNS sharing many similarities with MS. Demyelinat ion in MS is considered to be the result of an autoimmune process mediated by autoreactive T lymphocytes with specificity for myelin antigens. Methods : Phenotypic analysis and proliferation assays on blood monocytes, as well as isolation of myelin basic protein (MBP)-reactive T-cell lines/clones; an d TCR repertorium analysis by PCR-ELISA and cytokine production. Results: 1 ) The blood T-cell receptor (TCR) repertoire was compatible with in vivo ex pansion induced by S. pyogenes exotoxins, 2) TCR expression analysis indica ted clonal expansion of CD8(+) MBP-reactive T cells, suggesting in vivo act ivation. MBP-reactive T cells showed crossreactivity to S. pyogenes superna tant and exotoxins. 3) Cytokine mRNA quantification of the mononuclear cell s revealed a Th2-biased profile. Conclusion: In vivo exposure to S. pyogene s may have induced activation of pathogenic myelin reactive T cells, contri buting to the dramatic inflammatory demyelination.