Trio Wins Nobel Prize in Medicine for Immune-System Discoveries

“Immunologists Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi were awarded the Nobel Prize in Physiology or Medicine for uncovering a process that prevents the immune system from attacking our own tissues, called peripheral immune tolerance. The work unlocked a new field of research and potential therapies.

 

The three identified a core feature of how the immune system functions and keeps itself in check: regulatory T-cells. They prevent other immune cells from harming our own bodies and developing autoimmune conditions including Type 1 diabetes and rheumatoid arthritis. Based on this fundamental knowledge, clinical trials are testing therapies for autoimmune diseases, cancer and post-organ transplantation.

 

"Their discoveries have been decisive for our understanding of how the immune system functions and why we do not all develop serious autoimmune diseases," said Olle Kampe, chair of the Nobel Committee, on Monday.

 

Brunkow is now based at the Institute for Systems Biology in Seattle and Ramsdell at the San Francisco- and Seattle-based Sonoma Biotherapeutics, while Sakaguchi is a distinguished professor at Japan's Osaka University. The group will share the prize of 11 million Swedish kronor, equivalent to roughly $1.2 million.

 

Ramsdell, as far as anyone is aware, doesn't know he has won the prize yet; he is backpacking somewhere in Idaho, says Jeff Bluestone, chief executive of Sonoma Biotherapeutics. They last talked when Ramsdell was heading out on the trip in September. Bluestone said he has tried text, email and phone calls that have gone to voicemail.

 

"He is literally off the grid," Bluestone said.

 

Humans are constantly exposed to microbes that could make us sick, and the immune system developed to protect us. As part of this complex system, T-cells have receptors that help the body detect viruses, bacteria or other threats, but some can also attach to and alert against our own tissues, causing damage.

 

Researchers understood in the 1980s that T-cells mature in the thymus and undergo a test to eliminate cells that would latch on to our own tissues. Yet some can still escape into the bloodstream and become dangerous. Regulatory T-cells can keep these stray, potentially harmful cells in check.

 

"I first became interested in this field because I wanted to know more about how the immune system works, how your own body attacks itself," Sakaguchi said on Monday.

 

Sakaguchi made the first key finding while working at the Aichi Cancer Center Research Institute in Nagoya, Japan. His colleagues had discovered that removing the thymus in mice shortly after birth resulted in their immune systems' going haywire and the development of autoimmune diseases.

 

Sakaguchi then isolated mature T-cells from genetically identical mice and injected them into the mice without a thymus, and that appeared to protect them. The results of this trial and others convinced him that the immune system must include some cells that calm it down, and after a decade of work presented the new class of previously unknown immune cells in 1995, called regulatory T-cells.

 

American duo Brunkow and Ramsdell made a further key discovery in 2001, while working at a biotech company called Celltech Chiroscience in Bothell, Wash., that developed drugs for autoimmune conditions. They were looking at "scurfy" mice; males are unexpectedly born with flaky skin and enlarged spleens and live for only a few weeks, because their organs are attacked by their own immune cells.

 

Researchers suspected that the mutation causing the condition was somewhere on the X chromosome. The duo mapped a piece of chromosome from a scurfy mouse. They found the mutation on the final gene they checked, which they named the Foxp3 gene.

 

Later, they also discovered that mutations in the equivalent human gene caused a rare autoimmune disease, IPEX. Two years after that, Sakaguchi and later other researchers were able to prove that the Foxp3 gene controls the development of regulatory T-cells.

 

The laureates' discoveries have paved the way for research looking at forming more or modifying regulatory T-cells to fight autoimmune disease, as well as dismantling the co-opted T-cells that tumors use to hide from the immune system.” [1]

 

1. U.S. News: Trio Wins Nobel Prize in Medicine for Immune-System Discoveries. Abbott, Brianna; Fukutome, Junko; Vipers, Gareth.  Wall Street Journal, Eastern edition; New York, N.Y.. 07 Oct 2025: A3.