The role of T cells in Establishing Self-Tolerance

The human immune system is a powerful system designed to protect the individual from the onslaught of deleterious microorganisms that populate the natural environment.  Since it is essential that immune-capable cells not attack the tissues of the host, mechanisms for self-tolerance are necessarily implemented early in development.   When this self-tolerance mechanism fails, the result is often expressed as an autoimmune disease.  An example of such an ailment is multiple sclerosis (MS) in which the immune systems produces antibodies against myelin – the proteins that provides insulation for the electrical impulses that travel through the peripheral nerves.

Given the important role that self-tolerance plays in human health, many research laboratories are involved in fully elucidating its mechanism.   It is well known that the thymus gland is the site where self-tolerance is established.    It has also been shown that the immune regulator protein Aire is an important factor in the establishment of immunological tolerance; it operates within a subset of thymic stromal cells and directs T cell selection.  Aire is a transcription factor expressed in the medulla of the thymus and controls the mechanism that prevents the immune system from attacking the body itself.  Individuals with the autoimmune disease polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) have been shown to have a mutation in the AIRE gene.

Since Aire seems to play such a fundamental role in the early development of immuno-tolerance, it would be of extreme interest to delineate the underlying molecular mechanism for this affect.  Dr. Siyoung Yang and his colleagues at the Division of Immunology in the Department of Microbiology and Immunobiology at Harvard Medical School in Boston have made some interesting discoveries in this regard.  They have reported that Aire promotes the creation of a distinct population of regulatory T cells – Foxp3⁺CD4⁺ - in the very early stage of development.   Furthermore, they found that these regulatory T cells persist into adulthood and play a pivotal role in self-tolerance.

This is very important that contributes significantly to the understanding immune-tolerance and this kind information may prove invaluable in the understanding and eventual treatment of autoimmune diseases.