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From the Departments of Intensive Care Medicine (Drs. Jorens and Bossaert), Neurology (Dr. Ceulemans), Pediatrics (Dr. Van Bever), Microbiology (Drs. Ieven and Goossens), and Radiology (Dr. Parizel), University Hospital of Antwerp, Belgium; the Department of Microbiology (Dr. Van Dijk), Academisch Ziekenhuis Utrecht, University of Utrecht, the Netherlands; and the Biomedisch Onderzoeksinstituut DWI, Limburgs Universitair Centrum (Drs. VanderBorght, Raus, and Stinissen), Diepenbeek, Belgium.
Address correspondence and reprint requests to Dr. Philippe G. Jorens, University Hospital of Antwerp, Department of Intensive Care Medicine, Wilrijkstraat 10, B-2650 Edegem, Belgium; e-mail: philippe.jorens{at}uza.uia.ac.be
OBJECTIVE: After implicating Streptococcus pyogenes as causing acute disseminated encephalomyelitis (ADEM) in a child, we wanted to prove that in vivo activation of autoreactive T lymphocytes by superantigens of this Streptococcus contributed to the dramatic demyelination.
BACKGROUND: ADEM is a demyelinating disorder of the CNS sharing many similarities with MS. Demyelination 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; and TCR repertorium analysis by PCR-ELISA and cytokine production.
RESULTS: 1) The blood T-cell receptor (TCR) repertoire was compatible with in vivo expansion induced by S. pyogenes exotoxins. 2) TCR expression analysis indicated clonal expansion of CD8+ MBP-reactive T cells, suggesting in vivo activation. MBP-reactive T cells showed crossreactivity to S. pyogenes supernatant and exotoxins. 3) Cytokine mRNA quantification of the mononuclear cells revealed a Th2-biased profile.
CONCLUSION: In vivo exposure to S. pyogenes may have induced activation of pathogenic myelin reactive T cells, contributing to the dramatic inflammatory demyelination.
Key words: Acute disseminated encephalomyelitis—Autoimmune diseases—T lymphocytes—Streptococcus pyogenes—Exotoxins—Superantigens—MS—Demyelination—Myelin basic proteins—Experimental autoimmune encephalomyelitis
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