SENDING the immune system back to school and teaching it to tolerate foreign tissues could prevent transplants such as stem cells being rejected.
鈥淥ur strategy is simple: rewind the immune system back to its youth and re-educate it,鈥� says Richard Boyd of Monash University, Melbourne, whose team has discovered how to grow the thymus gland, a key part of the immune system. Now, with Alan Trounson鈥檚 team at the National Stem Cell Centre in Melbourne, he plans to use the technique to tackle immune rejection.
The thymus, located in the chest, is the schoolroom of the immune system, educating T cells to recognise the body鈥檚 own cells and not to attack them. Once that job is done, the thymus shuts down, shrinking from the size of an orange in a toddler to the size of a pea in middle age.
Advertisement
Boyd recently revealed that his team had found a way to grow thymuses in adult mice (Nature Immunology, vol 3, p 635). They found a type of cell in the thymus of mouse fetuses that, when grown outside the body and then placed in an adult mouse under its kidney capsule, can form a complete thymus.
In the next few months, Boyd told 快猫短视频, he and Trounson will grow more new thymuses in mice. But this time, they will introduce foreign cells, either when the thymus cells are growing in a dish, or after the new thymus has grown in the body. In theory, the immune system should then accept subsequent transplants of the foreign cells.
Not everyone is convinced. It might work for new T cells, but what are you going to do about the ones that are already circulating, asks Jacques Miller of the Walter and Eliza Hall Institute of Medical Research in Melbourne. 鈥淭hey鈥檝e been known to live for 50 years.鈥�
Boyd says the answer is to use drugs that destroy circulating T cells when the new thymus is growing. That would increase the risk of infections, but only for a short time. As the sex hormones produced from puberty onwards tell the thymus to shut down, it might also be necessary to temporarily suppress their levels, he says. Indeed, Boyd鈥檚 team is also investigating whether such chemical castration could help rejuvenate thymuses damaged by HIV or chemotherapy (快猫短视频, 19 December 1998, p 11).
However, it鈥檚 not yet clear if the progenitor cells used to grow the mouse thymuses are also found in adult humans. If they aren鈥檛, it might still be possible to grow non-matching thymuses from embryonic stem cells, but patients would have to be put on immunosuppressive drugs until the glands have grown and re-educated the immune system.
Even if it succeeds, the tolerising technique alone wouldn鈥檛 work for transplants from animals, since their tissues are so different. And because it takes months to grow the thymuses, it wouldn鈥檛 help with transplants where the donor isn鈥檛 known until the last minute, such as heart transplants. But it might work with stem cells.
Obtaining matched stem cells from patients is likely to be slow and very expensive. Another alternative, creating hundreds of stem cell lines, each with a different combination of immune system markers that could match any patient, is also likely to prove impractical. The tolerising technique could let doctors use cheap, 鈥渙ff-the-shelf鈥� stem lines.
It might also be used tore-educate the immune systems of people with autoimmune diseases. And even if the tolerising technique doesn鈥檛 prove effective, the designer thymuses could still be used to treat various diseases, such as DiGeorge syndrome, in which some people are born without a thymus gland.