Peacekeepers of the Immune System

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The idea of an immune system attacking its own tissues began about a hundred years ago by a bacteriologist named Paul Ehrlich. He gave it the name autoimmunity. Many medical experts believed that this was not possible until evidence was found, identifying several unsolved sicknesses as having this autoimmunity. The scientists discovered that these diseases are usually caused by rebellious white blood cells called CD4+ T lymphocytes, which mature in the thymus. Normally these cells fight off bacteria, but occasionally they mutiny against the other parts of the body. Cells that are specifically designed to stop this irregular behavior were also discovered. They are called regulatory T cells, and necessary for keeping the immune system in agreement with the body. These cells also affect the responses of the immune system to various things like cancer and organ transplants. The hope of the scientists is to find ways to control regulatory T cells in order to solve medical problems like diabetes, multiple sclerosis, and several others.

Researchers found that when proteins from an animal’s central nervous system were injected into the animal, along with a generalized immune system stimulus called an adjuvant, an awful reaction occurs. Other autoimmune diseases can occur by changing the source of the injected protein. This shows the large variety of tissue types that can be affected by autoimmunity. Researchers began to wonder why most animals and humans are not affected by autoimmunity and, after more tests, found many defense mechanisms that the immune system uses to prevent self-destruction. The first of these includes the development of T cells. In the thymus, all immature T cells are rigorously trained not to react harmfully to any of the body’s tissues. However, a few of these autoaggressive T cells manage to break out and escape into the bloodstream. The second defense deals with blood and lymph vessels. A small amount of these vessels penetrating deep into tissues helps to isolate cells that could cause autoimmunity. A third way involves healthy immune system cells targeting these cells and destroying them or causing them to become inactive.

The existence of regulatory T cells dates back to the 1960’s, when removing the thymus from young female mice resulted in the mice losing their ovaries. The researchers first believed the idea of some hormone that was secreted from the thymus and necessary in order for the ovaries to develop. Then it was discovered that immune system cells were attacking the ovaries. When the mice received a vaccine of normal T cells, the disease was repressed.
A few years later, it was proposed that these T cells might be able to diminish immune responses. Scientists began looking for a “marker” in order to distinguish T cells that could prevent autoimmunity. In 1995, Sakaguchi experimented with a molecule called CD25, and proved it to be a dependable marker. When CD4+ T cells exhibiting the molecule were removed from mice, inflammation occurred in the stomach, thyroid, pancreas, gonads, and salivary glands, confirming that the body was under an autoimmune attack. Also depriving certain mice without immune systems of their CD4+ T cells containing CD25 caused autoimmunity, and the greater the depletion, the worse the diseases that resulted. These cells are now being called CD 25+ regulatory T cells, or T-regs.

How T-regs function and develop is still somewhat of a mystery. Recently, it was revealed that T-regs contain a large amount of a molecule called Foxp3. Foxp3 regulates the activity of specific genes, basically controlling the system of the protein production, and modifying proteins can affect how a cell functions. Foxp3 has been reported to transform T cells into T-regs by the changes it brings in gene activity. Foxp3 was studied in rodents, but it is also present in great amounts in human T-reg cells. One major indication that Foxp3 is crucial for human health comes from a rare genetic disorder known as IPEX. IPEX involves a mutation in a gene on the X chromosome and is seen in male children who only have one X chromosome and do not have a normal duplicate. This mutation causes severe autoimmune disease leading to very early death. New proof states that this is a mutation in Foxp3.

Evidence shows that T-regs do not prevent autoimmune disease in people, but they do seem to aid health in other ways. One study involved transferring T cells not containing T-regs into mice without immune systems. Some mice received a deadly form of inflammatory bowel disease, but the immune system’s activity was not primarily focused upon the bowel tissue. The bowels of animals and humans contain huge amounts of foreign bacteria, which actually prove to be helpful, aiding in the digestion of food and take the place of harmful bacteria that would try to invade the intestines. In these mice, the immune system attacked the harmful bacteria, causing the bowel to become swollen. Yet when T-regs were transferred with the other T cells, the bowel disease was avoided.

T-regs may also affect responses to dangerous foreign cells. It is possible that they could prevent an invader from being fully destroyed, allowing it to break out again. However this may not altogether be a bad thing. When the immune system was left unharmed in the mice, the response to the reinfection was quick and efficient. When the immune system was deprived of its T-regs, the body rid itself completely of the invader, yet reinfection was not swift or efficient. Therefore we see how T-regs contribute to keeping immunological memory, a process that the success of vaccination depends on. T-regs are useful in protecting pregnancies. The baby is basically considered to be an organ transplant to the immune system because half of its genes come from its father. Placental tissue called the trophoblast protects the baby from autoimmunity by way of the mother’s blood and produces molecules to suppress autoimmune disease. It has also been reported that T-regs become more active in women during pregnancy. Scientists contemplate if a great enough decrease in T-reg activity could cause the reappearance of unexpected abortion.

Medicine that changes the activity of T-regs has strong potential for being used to help regulate immune responses in the future. Experiments are being conducted and scientists are trying to find ways to solve diseases by altering the actions of T-regs as well as the number of T-regs. Increasing T-reg activity may eventually be used to cure allergies, avert organ transplant rejection, and even allow grafts to be tolerated better. Decreasing T-reg activity could perhaps help in diseases, like AIDS and tuberculosis, where the immune system cannot fight effectively by itself. A treatment for cancer could also be discovered by T-reg depletion. T-regs are believed to hinder immune cells that would destroy cancerous cells, and in a way inadvertently help the cancer spread. Research implies that cancer patients have unusually high levels of active T-regs, and that some cancerous cells secrete signals that draw T-regs to them and even transform non T-regs into T-regs.

Scientists are having many challenges trying to create medicines that would make a change in T-regs, mainly because they do not know which T-regs to pursue. T-regs are very rare cells; so obtaining millions of them needed to prevent autoimmune disease could be impossible. By treating regular T cells with certain biochemical signals, researchers have created what they call Tr1 cells, that are thought to be identical to T-regs. These Tr1 cells are definitely immunosuppressive. Foxp3 is also being examined, since it was discovered to be a main component for managing the development and function of T-regs. Researchers are also trying to figure out ways to transfer Foxp3 into more easily accessible T cells, so T-reg cells could be developed. Methods of distinguishing molecular events that trigger the production of Foxp3 are also being investigated. In regard to organ transplants, T-regs could be taken from the patient who will receive the transplant and cultivated with cells from the organ donor, causing T-regs that will help restrain the rejection to multiply. This has been accomplished in rodents and is expected to work for humans also.

Scientists’ understanding of the immune system has drastically changed over the past few years. They have discovered T cells and see their autodestructive and immunosuppressive capabilities. Learning more about how they develop and carry out their actions will help scientists find ways to used them for preventing certain diseases and disorders. T-regs may eventually be considered to be vital immunological peacekeepers.

This article contains very helpful and thorough information about T-cells and how they help against autoimmune disease. It provides proof for its statements by backing them up with experiments that were conducted. It also explains what makes T-regs so necessary and the certain markers that are seen in T cells. It talks about diseases that could be cured by altering T-regs, but it seems like much more investigation is needed before these treatments can be found. With time, research, and patience, more clues should eventually unfold.