Thymic mimetic cells: tolerogenic masqueraders

Medullary thymic epithelial cells (mTECs) clonally delete or divert autoreactive T cells by ectopically expressing a diverse array of peripheral-tissue antigens (PTAs) within the thymus. Although thymic stromal cells with histological features of extra-thymic cell types, like myocytes or neurons, have been observed by light microscopy since the mid-1800s, most modern work on PTA expression has focused on the transcription factor Aire. Here, we highlight recent work that has refocused attention on such 'misplaced' thymic cells, referred to collectively as thymic mimetic cells. We review the molecular underpinnings of mimetic cells and their roles in establishing T cell tolerance, and we propose that mimetic cells play important roles in autoimmunity. Finally, we suggest future directions for this emerging area.