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.

Long Term Effects of Measles Infection on the Immune System

It is a well-established that contraction of measles has a lasting impact on the immune system predisposing the individuals affected to opportunistic infections.  The period of vulnerability was thought to last for months.  In fact, it has recently been shown that this deleterious impact on the host’s immune system can persist for over 2 to 3 years.  This is of particular concern to public health professionals especially in those parts of the world where the measles immunization regimen is poorly administered or in those regions where there is a complete lack of infrastructure for the delivery of health care.  Public health data shows that wherever mass measles immunizations are employed childhood mortality is lowered by 30 to 50% in so-called resource-poor countries and up to 90% for impoverished populations.

It has been of interest to determine the mechanistic explanation for this apparent lost in immune-competency in individuals infected by the measles virus.  The suspicion has been that measles infection results in the loss of the host’s immune system memory-cell population – a condition referred to as “immune amnesia.”

Dr. Michael J. Mina and his colleagues at the Department of Ecology and Evolutionary Biology at Princeton University, Princeton NJ were able to confirm through epidemiological data that, in fact, measles infection leads to the ablation of those T and B lymphocytes responsible for immunological memory thereby leaving patients susceptible to opportunistic infections.  Children in this group are particularly prone to increased mortality in this setting.

In addition, the data also unambiguously demonstrated the efficacy of measles vaccination in preventing potentially lethal opportunistic infections that would otherwise spread through susceptible populations impacted by uncontrolled measles infections.  These finding are of particular interest in terms of improving public health on a global basis.