Experimental myasthenia gravis in Aire-deficient mice: a link between Aire and regulatory T cells

摘要

Aire (autoimmune regulator) has a key role in the establishment of tolerance to autoantigens. Aire?/? mice present decreased thymicexpression ofAChR, significantly lower frequenciesof regulatoryT(T_(reg)) cells, andhigher expression of Th17 markers, compared to controls. We therefore predicted that Aire?/? mice would be more susceptible to induction of experimental autoimmune myasthenia gravis (EAMG). However, when EAMG was induced in young mice, Aire?/? mice presented a milder disease that wild-type (WT) controls. In contrast, when EAMG was induced in older mice, Aire?/? mice were more severely affected than WT mice. The relative resistance to EAMG in young Aire?/? mice correlated with increased numbers of T_(reg) cells in their spleens compared to young controls. A similar age-related susceptibility was also observed when EAE was induced in Aire?/? mice, suggesting an age-related link among Aire, disease susceptibility, and peripheral T_(reg) cells that may be a general feature of autoimmunity.