Viral infection triggers central nervous system autoimmunity
Nature Immunology | Article
Viral infection triggers central nervous system autoimmunity via
activation of CD8+ T cells expressing dual TCRs
· _Qingyong Ji_ (javascript:;) ,
· _Antoine Perchellet_ (javascript:;)
· & _Joan M Goverman_ (javascript:;)
Journal name:
Nature Immunology
Volume:
11,
Pages:
628–634
Year published:
(2010)
DOI:
doi:10.1038/ni.1888
Received
30 March 2010
Accepted
13 May 2010
Published online
06 June 2010
Abstract
Multiple sclerosis is an inflammatory, demyelinating, central nervous
system disease mediated by myelin-specific T cells. Environmental triggers that
cause the breakdown of myelin-specific T cell tolerance are unknown.
Here we found that CD8+ myelin basic protein (MBP)-specific T cell
tolerance was broken and autoimmunity was induced by infection with a virus that
did not express MBP cross-reactive epitopes and did not depend on bystander
activation.
Instead, the virus activated T cells expressing dual T cell antigen
receptors (TCRs) that were able to recognize both MBP and viral antigens. Our
results demonstrate the importance of dual TCR–expressing T cells in
autoimmunity and suggest a mechanism by which a ubiquitous viral infection could
trigger autoimmunity in a subset of infected people, as suggested by the
etiology of multiple sclerosis
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