Selection of Aire-dependent thymic regulatory T cells by CD8α+ dendritic cells. Thymic Treg TCR sequencing

The contribution of individual thymic antigen presenting cell (APC) subsets to T cell tolerance remains unknown. We show that bone marrow (BM) APCs and medullary thymic epithelial cells (mTECs) play non-redundant roles in shaping the TCR repertoire via deletion and regulatory T cell (Treg) selection. Interestingly, a substantial number of Treg cells were selected via a pathway dependent on antigen presentation by BM APCs and Aire expression in mTECs. CD8α+ dendritic cells (DCs) were the crucial BM APC in this pathway, showing enhanced ability to acquire and present antigens from stromal cells. Thus, these data reveal the interconnected nature of the thymic APC network mediated by mTECs and CD8α+ DCs that collaboratively shapes the self-tolerant TCR repertoire.