United Press International - June 21, 2002
Stephen Sheldon

The thymus is a small organ crucial to the human immune system. Located above the heart, it creates, programs and distributes special white cells known as T-cells -- the "T" is for thymus-derived lymphocytes -- which fight infection by reacting against foreign organisms and tissues. It is the key to good health because, without it, the body has no protection against viruses.

"It's one of the least glamorous but most essential organs," Dr. Jason Gill, an immunologist at Monash University and one of the lead researchers, told United Press International.

The thymus also is one of the strangest. In a child, the thymus is as big as an apple and, in most individuals, fully functional. Children replenish their blood with T-cells very efficiently. Yet at puberty, due to the onset of huge levels of sex steroids, the thymus shrivels to peanut size and drops in efficiency. Researchers theorize this might be why many auto-immune diseases, such as multiple sclerosis, cancers and diabetes, increase in adults.

The team leader, immunologist Richard Boyd, told UPI his inspiration for the project began 20 years ago when he wondered if it would be possible to boost the immune system by manipulating and activating the thymus to make it function better. The first step, he said, involved a quest to identify the stem cells in the thymus. Stem cells are the body's building blocks and have unlimited capacity to grow and replace all the cells within a particular tissue or organ.

Boyd's next step was to insert thymus stem cells from the embryonic material of one mouse into the kidney cavity of its identical twin. There, the stem cells grew into a functioning thymus -- the first time anyone had generated a fully functional organ grown from a few stem cells.

The main significance of the research, Boyd said, is the ability to create T-cells, which could lead to treatments for conditions in which the cells have been severely depleted, such as AIDS, and after radiation therapy, chemotherapy and bone marrow transplants.

Generating new T-cells also could be useful in correcting auto-immune diseases, which are caused by abnormal T-cells from a malfunctioning thymus, he said. It also might lead to an opportunity to rebuild a patient's thymus after it has been destroyed.

The researchers now are proceeding down several avenues, Boyd said. First is to see whether they can grow a thymus from stem cells taken from an adult mouse. If they can, they hope to be able to re-stimulate the thymus to grow more T-cells.

They also are seeking to identify thymus stem cells in humans and they are hoping to begin human clinical trials within two years on therapies to create a fully functional thymus.

The man credited with discovering the function of the thymus back in 1961, Emeritus Professor Jacques Mille, now at Melbourne's Walter and Eliza Hall Institute, told UPI although the work will one day "prove very useful" it is too early for medical research to claim a triumph over disease.

"The work is excellent and the identification of stem cells, and the growth of a thymus from these cells, are certainly an advance," Mille said. "But the work does not solve the puzzle of how to transplant an organ, in this case the thymus, from one animal to another without it being rejected by the recipient. That is still the holy grail."

Mille added, "So far, the research has only been done on identical mice, which is the only way it can be successfully done without the use of drugs to suppress the body's immune response."

The findings are published in this week's issue of the journal Nature Immunology.

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