We are constantly exposed to foreign agents in the environment, such as bacteria, viruses and allergens, which can make us sick. But, although we are seldom aware of it, our immune system is constantly working to protect us. However, sometimes the immune system turns against our own cells and organs, falsely recognizing them as foreign and mounting an attack against them. Such an unwanted immune response is known as autoimmunity and some examples of autoimmune diseases include lupus, multiple sclerosis, type 1 diabetes, inflammatory bowel disease, and rheumatoid arthritis. Current research is focused on understanding the causes of autoimmune diseases as well as on the development of better therapies. Recent research published in the June issue of Gastroenterology describes a new method which might someday be used to treat inflammatory bowel disease. Excitingly, this method might also be adapted for use against a wide range of other autoimmune disorders, increasing the quality of life for individuals who suffer from the devastating effects of autoimmune diseases.

The Immune System: the Body’s Army Against Foreign Invaders

If you imagine your body to be a nation, you can think of your immune system as a military, functioning to protect you from threats and invaders. And, just as the military of a nation is divided into different branches or forces (such as the army, navy, marines, etc.) so is the immune system divided into specialized branches. Each of these branches has a specific function, but all collaborate with each other in order to patrol and protect the body. Among the immune system’s forces are B and T cells, both of which are circulating white blood cells. B cells make proteins, called antibodies, which can tag foreign agents (like bacteria) for elimination. T cells can directly attack or kill foreign agents.

The immune system has the amazing ability to distinguish one’s own tissues, or ‘self’, from foreign agents or ‘non-self’. In order to be able to do this, the immune system, like any military, must undergo training or education. In a healthy individual, the cells that form the different branches of the immune system undergo an educational process during their development in which cells that strongly recognize ‘self’ are eliminated. If an immune cell that reacts strongly against ‘self’ escapes elimination, other mechanisms exist throughout the body that can eliminate or suppress autoimmune attack by such escapees. Among these mechanisms are a small group of cells called regulatory T cells, or T-regs. These cells can render escapees incapable of attacking the body’s own organs and tissues. Eliminating or suppressing cells that react against ‘self’ is important since these cells have a great potential to cause extensive damage to our organs. When these cells are not successfully eliminated or suppressed, this leads to an inappropriate immune response against ‘self’ resulting in autoimmune disease.

T-regs to the Rescue

Inflammatory bowel disease (IBD) is a type of autoimmune disorder in which the circulating white blood cells that make up the immune system migrate to the intestine recognizing it as foreign or ‘non-self’; this process is what causes unwanted inflammation of the intestine. Depending on the type and severity, some of the symptoms of IBD include abdominal pain, diarrhea, and weight loss. Previous studies have shown that T-regs are essential for the maintenance of normal intestinal immune responses and for the protection from intestinal autoimmunity, such as in IBD. However, previous attempts at using T-regs to suppress autoimmune intestinal inflammation have been hampered by the inability to direct a sufficient number of T-regs to the site of inflammation. In order to overcome this, scientists from the Weizmann Institute in Rehovot, Israel developed genetically engineered T-regs that specifically migrate to, accumulate, and become activated in the intestine. In laboratory mice, treatment with the genetically engineered T-regs was able to prevent a disease similar to human IBD as well as to significantly reduce existing inflammation in the intestine. Interestingly, some mice had almost no inflammation at all after treatment with these novel T-regs. In addition, the researchers found that the T-regs are directed to the intestine by signals that identify the organ as a site of inflammation and that, once the cells reached the intestine, they suppressed inflammation by secreting suppressive substances that can deactivate immune cells that are reacting against the intestine.

A promising new treatment for autoimmune disease

The scientists are now using human T-regs in experiments aimed to cure IBD in patients. In addition, further studies are being conducted to develop more efficient methods of harvesting, expanding, and genetically manipulating a sufficient number of a patient’s own T-regs for subsequent administration as well as to improve the stability of these cells once administered to the patient. Importantly, the researchers believe that T-regs can be genetically engineered to control other types of autoimmune disorders, even in cases where the underlying cause is unknown. Furthermore, this method might also be useful in preventing transplant organ rejection.

Currently the causes of autoimmunity are obscure, although research has shown that some patients may have a genetic predisposition for autoimmune disease. Until researchers can provide a better understanding of the genetic and environmental factors that trigger autoimmune diseases, and thereby shed light on prevention tactics, the search is on for ways to improve upon the therapies that are currently available. Research like that done at the Weizmann Institute suggests that enlisting and retraining the body’s own military personnel might be one effective strategy.

–Erika D. Reynoso, Harvard Medical School

For More Information:

Science Daily’s coverage of this research:
< http://www.sciencedaily.com/releases/2008/06/080602103348.htm >

The Weizman Institute home page:
< http://www.weizmann.ac.il/ >

Information on autoimmune disease from the National Institutes of Health:
< http://www.nlm.nih.gov/medlineplus/autoimmunediseases.html >

Primary Literature:

Elinav, E. et al. 2008. Redirection of regulatory T cells with predetermined specificity for the treatment of experimental colitis in mice. Gastroenterology. 134(7): 2014-2024.

Zoeten and Hancock. 2008. Strategies to cure experimental autoimmune colitis using antige-specific Foxp3+ regulatory T cells. Gastroenterology. 134 (7): 2171-2174.

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