Encephalomyelitis-associated antimyelin autoreactivity induced by streptococcal exotoxins.
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.


CONCLUSIONS
In vivo exposure to S. pyogenes may have induced activation of pathogenic myelin reactive T cells, contributing to the dramatic inflammatory demyelination.
Jorens
P G
PG
Department of Intensive Care Medicine, University Hospital of Antwerp, Belgium. philippe.jorens@uza.uia.ac.be
VanderBorght
A
A
Ceulemans
B
B
Van Bever
H P
HP
Bossaert
L L
LL
Ieven
M
M
Goossens
H
H
Parizel
P M
PM
Van Dijk
H
H
Raus
J
J
Stinissen
P
P
D015551:Autoimmunity / Q000276:immunology*; D001921:Brain / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D002675:Child, Preschool; D003429:Cross Reactions / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004673:Encephalomyelitis, Acute Disseminated / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D005098:Exotoxins / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D008279:Magnetic Resonance Imaging; D008297:Male; D004676:Myelin Basic Protein / Q000276:immunology; D009186:Myelin Sheath / Q000276:immunology*; D011782:Quadriplegia / Q000209:etiology; D013290:Streptococcal Infections / Q000175:diagnosis / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000302:isolation & purification*; D018089:Superantigens / Q000276:immunology
D016207:Cytokines; D005098:Exotoxins; D004676:Myelin Basic Protein; D018089:Superantigens