Stockholm: Mary E. Brunkow and Fred Ramsdell of the United States and Japan's Shimon Sakaguchi won the Nobel Prize in Medicine on Monday for research into how the immune system is kept in check, the Nobel jury said.

Their discoveries have been decisive for understanding how the immune system functions and why we do not all develop serious autoimmune diseases.

The three were honoured "for their discoveries concerning peripheral immune tolerance", the jury said.

"Their discoveries have laid the foundation for a new field of research and spurred the development of new treatments, for example for cancer and autoimmune diseases," it added.

Their findings may also lead to more successful transplantations.

Sakaguchi, 74, made the first key discovery in 1995.

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At the time, many researchers were convinced that immune tolerance only developed due to potentially harmful immune cells being eliminated in the thymus, through a process called "central tolerance".

Sakaguchi showed that the immune system is more complex and discovered a previously unknown class of immune cells, which protect the body from autoimmune diseases.

Brunkow, born in 1961, and Ramsdell, 64, made the other key discovery in 2001, when they were able to explain why certain mice were particularly vulnerable to autoimmune diseases.

"They had discovered that mice have a mutation in a gene that they named Foxp3," the jury said.

"They also showed that mutations in the human equivalent of this gene cause a serious autoimmune disease, IPEX."

Two years later, Sakaguchi was able to link these discoveries.

The trio will receive their prize -- a diploma, a gold medal and a $1.2-million cheque -- from King Carl XVI Gustaf at a formal ceremony in Stockholm on December 10, the anniversary of the death in 1896 of scientist Alfred Nobel.

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