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

Aire (autoimmune regulator) has a key role in the establishment of tolerance to autoantigens. Aire(-/-) mice present decreased thymic expression of AChR, significantly lower frequencies of regulatoryT(T-reg) cells, and higher 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.