Mary Brunkow is a researcher at the Institute for Systems Biology in Seattle, Fred Ramsdell works for the biotechnology company Sonoma Biotherapeutics based in San Francisco, and Shimon Sakaguchi is a scientist at Osaka University in Japan.
Following their discoveries, they identified a mechanism that helps the body keep the immune system "in check" so that it does not turn against its own cells.
Specifically, they revealed the key role of so-called regulatory T cells and the FOXP3 gene, which are essential for maintaining the balance between protection and self-harm in our bodies. For this, they were awarded the Nobel Prize in Physiology or Medicine for 2025.
The immune system – protector and potential enemy
The immune system is a complex network of cells, organs, and molecules that protects the body from viruses, bacteria, and parasites. When a foreign organism enters the body, immune cells recognize and destroy it.
One of the main groups of these cells are T cells – derived from the thymus, where they mature.
However, their activity must be very precisely controlled. If the immune system "makes a mistake" and starts attacking its own tissues, autoimmune diseases such as rheumatoid arthritis, type 1 diabetes, or multiple sclerosis develop.
Our body has several defense mechanisms that limit these mistakes.
The thymus tests whether young T cells recognize their own tissues. If they do, the thymus destroys most of them. However, this process is imperfect, and some "defective" cells can escape into the body.
T cells that inhibit others
In the 1990s, Japanese immunologist Shimon Sakaguchi studied how the body prevents these escaped T cells from causing damage.
After a series of experiments on mice, he discovered that there is a special type of T cell in the body that acts as a kind of peacemaker. They oversee the activity of other immune cells in the body and suppress excessive immune responses that could lead to autoimmune diseases.
He recognized these "braking" cells by a unique surface marker, the CD25 protein, and called them regulatory T cells. When Sakaguchi removed these cells from the bodies of mice, their immune systems went haywire—they began attacking their own tissues and caused widespread inflammation.
Sakaguchi published his discovery in 1995 in the prestigious Journal of Immunology, but the scientific community was initially skeptical. Confirming evidence came several years later thanks to Brunkow and Ramsdell.
The gene that controls regulatory T cells
In 2001, these two American scientists studied mice suffering from severe autoimmune diseases and searched for the genetic causes of this condition.
They found that the problem was related to a defect in the FOXP3 gene on the X chromosome. Mice with a mutation in this gene had a completely disrupted immune system and died of severe inflammation. Brunkow and Ramsdell subsequently discovered similar mutations in humans, specifically in boys suffering from a rare but fatal autoimmune disease called IPEX syndrome.
Their research showed that the FOXP3 gene acts as a master switch that triggers the development of regulatory T cells. Without it, these cells do not develop—and the immune system loses its brake.
This discovery definitively confirmed Sakaguchi's hypothesis and created a new concept that we now know as peripheral immune tolerance. This prevents the immune system from damaging its own body.
"Their discoveries were crucial to our understanding of how the immune system works and why not all people develop serious autoimmune diseases," said Olle Kämpe, chairman of the Nobel Committee.
The importance of the discovery
The discoveries of the three laureates laid the foundations for a new field of research known as peripheral immune tolerance and stimulated the development of therapies targeting regulatory T cells in areas such as cancer, autoimmune diseases, and stem cell transplantation.
Currently, more than 200 clinical studies based on their research are underway.
Brunkow, Ramsdell, and Sakaguchi will share the Nobel Prize worth $1.2 million.