In this issue of Nature Immunology, Goverman and colleagues present an intricate series of experiments whose results identify a previously unknown mechanism by which T cell antigen receptor (TCR)-transgenic CD8~+ anti-myelin T cells can be induced to break tolerance and cause severe demyelination1. Although me model relies on cutting-edge technology and an engineered immune system, the underlying scheme shown here may be surprisingly relevant for the pathogenesis of the most prevalent human demyelinating disease, multiple sclerosis.
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