T lymphocytes require education in order to distinguish between self and nonself. This education is maintained by thymus stromal epithelial expressing the autoimmune regulator gene (AIRE). These cells express proteins from throughout the organism not in promotor regulated way, but in a epigenetically controlled statistically mode, the only cells that do so. This has as a consequence that these cells present on their surface each a part of the possible plethora of self peptides in the context of MHC class I molecule. T cells which react with them do recognize self and should be suppressed lifelong to avoid autoimmunity.

In a paper by Yang and colleagues from the Benoist/Mathis laboratory at Stanford it is now reported, that early regulatory T cells are additionally required to maintain the protection against autoimmune diseases. If the cells are lacking due to the absece of AIRE expression, a disease called autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy or
autoimmune polyglandular syndrome 1 is the consequence. The News and Views contribution by Tanaka and Sakaguchi explains this in detail.  This is a nice addition to the problem of tolerance and and might be an important step to development of tolerance to foreign antigens as well. That would be required to make gene therapy sustainable.

A must!