Expression of Self-antigen in the Thymus : A Little Goes a Long Way

For many years, it has been hypothesized that a major factor in organ-specific autoimmunity is a lack of central tolerance to self-antigens that are sequestered behind anatomical barriers in organs such as the eye, testis, and brain. However, numerous studies published in the last few years argue strongly that this concept of sequestration of tissue-specific antigens in such immune-privileged organs should be revised. Many tissue-specific antigens are now known to be expressed in the thymus (for review see 1) primarily in medullary thymic epithelial cells (mTECs) (2), which appear to be a specialized subset of cells that may mediate deletion of self-reactive T cells and/or the induction of regulatory T cells (Tregs). Genetic analysis of a group of human autoimmune diseases known as autoimmune polyendocrinopathy-candidiasis-ectodermaldystrophy (APECED) has shown that the expression of tissue antigens in mTECs may be mediated by a transcription...