Tissue restricted antigen expression by medullary thymic epithelial cell subsets induces distinct autoreactive T cell fates

Cellular interactions in the thymus play an essential role in ensuring the development of a self-tolerant T cell repertoire. Medullary thymic epithelial cells (mTECs) contribute to tolerance by expressing and presenting tissue-restricted antigens (TRA) so that developing T cells can assess the self-reactivity of their antigen receptors prior to leaving the thymus. This has largely been studied in the context of autoimmune regulator (Aire) dependent TRA expression in mature mTECs. Yet, mTECs are a heterogeneous population of cells that differentially express unique pools of TRA, and whether mTEC subsets induce distinct autoreactive T cell fates remains unclear. Here we attribute unique roles for mTEC subsets in directing distinct mechanisms of T cell tolerance that significantly impact infection and tumor control. These results have important implications in the design of effective therapeutic approaches that aim to modulate the function of self-reactive T cells. Thymic epithelial cells were sorted from CRPhi, CRPlo and INShi transgenic mice