Immunology

Too Much Recognition

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Science  13 Aug 2010:
Vol. 329, Issue 5993, pp. 729
DOI: 10.1126/science.329.5993.729-b

Multiple sclerosis is an autoimmune disease of the central nervous system; normally tolerant T cells attack the myelin sheaths that surround nerve fibers. Although some viruses have been fingered as environmental triggers of the disease, how they would cause multiple sclerosis has not been established. Ji et al. show that CD8+ T cells that express two antigen receptors with distinct specificities can drive the development of a virus-induced, multiple sclerosis–like condition [experimental autoimmune encephalitis (EAE)] in mice. The authors used mice whose CD8+ T cells expressed a transgenic antigen receptor that specifically recognized myelin basic protein. These mice did not spontaneously develop autoimmunity, but infection with vaccinia virus that had been engineered to express recombinant myelin basic protein did trigger the onset of EAE. Surprisingly, viral expression of myelin basic protein was not required because mice infected with wild-type vaccinia virus also developed EAE, and the authors found that EAE only developed in mice whose T cells were of dual specificity. That is, the engagement of the endogenous T cell receptors by virus leads to T cell activation, but because these T cells can also recognize myelin basic protein, they then promote EAE development. Similar results were seen when mice were infected with adenovirus, indicating that viral infections generally could promote the development of multiple sclerosis in some of the infected individuals.

Nat. Immunol. 11, 628 (2010).

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