Mary E. Brunkow, Fred Ramsdell and Dr. Shimon Sakaguchi won the Nobel Prize in medicine Monday for their discoveries concerning peripheral immune tolerance.

Brunkow, 64, is a senior program manager at the Institute for Systems Biology in Seattle. Ramsdell, 64, is a scientific adviser for Sonoma Biotherapeutics in San Francisco. Sakaguchi, 74, is a distinguished professor at the Immunology Frontier Research Center at Osaka University in Japan.

The immune system has many overlapping systems to detect and fight bacteria, viruses and other intruders. Key immune warriors such as T cells get trained on how to spot bad actors. If some instead go awry in a way that might trigger autoimmune diseases, they’re supposed to be eliminated in the thymus — a process called central tolerance.

The Nobel winners unraveled an additional way the body keeps the system in check.

"It's an honor to have been part of that initial work," said Brunkow.

Brunkow got the news of her prize from an AP photographer who came to her Seattle home in the early hours of the morning.

The Nobel Committee said it started with Sakaguchi’s discovery in 1995 of a previously unknown T cell subtype now known as regulatory T cells or T-regs. Then in 2001, Brunkow and Ramsdell discovered a culprit mutation in a gene named Foxp3, a gene that also plays a role in a rare human autoimmune disease.

Brunkow said she and Ramsdell were working together at a biotech company, investigating why a particular strain of mice had an over-active immune system. They had to work with brand-new techniques to find the mouse gene behind the problem — but quickly realized it could be a major player in human health, too.

“From a DNA level, it was a really small alteration that caused this massive change to how the immune system works,” Brunkow said.

The work opened a new field of immunology, said Karolinska Institute rheumatology professor Marie Wahren-Herlenius. Researchers around the world now are working to use regulatory T cells to develop treatments for autoimmune diseases and cancer.

"By winning the prize, I hope this research field develops further, and be applied in a clinical setting. I hope we can contribute to it, too," said Shimon Sakaguchi.

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