More mature and more promiscuous

Epithelial cells in the thymus teach T cells what to ignore by presenting them with a comprehensive array of tissue-restricted self-antigens (TRAs) during development. According to Derbinski and colleagues on page 33, this promiscuous expression of TRAs—one of the mechanisms behind central T cell tolerance—increases as the epithelial cells mature.

Teaching T cells how to distinguish self-tissues from foreign invaders is essential for the prevention of autoimmune disease. This education process occurs in the thymus and depends on the presentation of a diverse array of self-antigens to developing thymocytes—a function of medullary thymic epithelial cells (mTECs). T cells that recognize these self-antigens are either deleted or become regulatory T cells.

Recent studies have shown that the transcriptional regulator Aire (autoimmune regulator), which is highly expressed in mTECs, drives the...