Aire regulates the transfer of antigen from mTECs to dendritic cells for induction of thymic tolerance

Abstract

To investigate the role of Aire in thymic selection, we examined the cellular requirements for generation of ovalbumin (OVA)-specific CD4 and CD8 T cells in mice expressing OVAunder the control of the rat insulin promoter. Aire deficiency reduced the number of mature single-positive OVA-specific CD4 + or CD8+T cells in the thymus, independent of OVA expression. Importantly, it also contributed in 2 ways to OVA-dependent negative selection depending on the T-cell type. Aire-dependent negative selection of OVA-specific CD8 T cells correlated with Aire-regulated expression of OVA. By contrast, for OVA-specific CD4 T cells, Aire affected tolerance induction by a mechanism that operated independe..