The laureates identified the immune system's security guards, regulatory T cells, thus laying the foundation for a new field of research.
Published Oct 07, 2025 | 7:00 AM ⚊ Updated Oct 07, 2025 | 7:00 AM
How three scientists discovered why our bodies don't destroy themselves. (Supplied)
Synopsis: On Monday, three scientists—Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi—received the 2025 Nobel Prize in Physiology or Medicine for finally answering this question. They discovered the body’s secret security guards: Special cells that constantly patrol your body, making sure your defence system doesn’t accidentally destroy you.
Imagine your body as a fortress under constant siege. Every single day, thousands of different viruses, bacteria and other microbes attempt to invade. Your immune system is the army defending this fortress—and it’s incredibly good at its job. Without it, you would not survive.
But here’s the terrifying part: this army is so powerful, so aggressive, that without something to control it, it would turn its weapons on the fortress itself and tear it apart from the inside.
The question that has puzzled scientists for decades is breathtakingly simple: Why doesn’t the immune system attack our bodies more frequently?
On Monday, three scientists—Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi—received the 2025 Nobel Prize in Physiology or Medicine for finally answering this question. They discovered the body’s secret security guards: Special cells that constantly patrol your body, making sure your defence system doesn’t accidentally destroy you.
“Their discoveries have been decisive for our understanding of how the immune system functions and why we do not all develop serious autoimmune diseases,” says Olle Kämpe, chair of the Nobel Committee.
This is their story.
BREAKING NEWS
The 2025 #NobelPrize in Physiology or Medicine has been awarded to Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi “for their discoveries concerning peripheral immune tolerance.” pic.twitter.com/nhjxJSoZEr— The Nobel Prize (@NobelPrize) October 6, 2025
Our story begins in the 1980s, when most scientists thought they had already solved the puzzle. They believed the answer lay in something called the thymus—a small organ in your chest that acts like a military training camp for immune cells.
Think of it this way: Your body creates millions of different soldier cells (called T cells) that can recognize almost any threat. But the body accidentally also creates soldiers programmed to attack your own tissues. Scientists believed these “rogue soldiers” were eliminated during boot camp in the thymus through a process called central tolerance. Case closed.
Some researchers suspected there might be another layer of protection—cells they called “suppressor” cells. But this idea had become toxic in the scientific community. Some researchers had made false claims, and when the evidence fell apart, the entire hypothesis was rejected. The research field was more or less abandoned.
But one man refused to let it go. His name was Shimon Sakaguchi, and he worked in Nagoya, Japan.
Sakaguchi was inspired by a bizarre experiment. His colleagues had removed the thymus from newborn mice, expecting them to have weaker immune systems. But when the operation took place three days after the mice were born, something shocking happened: the immune system went into overdrive and ran amok, attacking everything in sight. The mice developed a range of autoimmune diseases—their bodies literally destroying themselves.
This didn’t make sense. If the thymus was the only thing preventing self-attack, why would removing it make things worse?
At the start of the 1980s, Sakaguchi tested a wild idea. He took healthy immune cells from normal mice and injected them into the mice without a thymus. The result stunned him: there appeared to be cells that could protect the mice from autoimmune diseases. These cells were like peacekeepers, calming down the aggressive soldiers.
Sakaguchi became convinced that the immune system must have some form of security guard, one that calms down other cells and keeps them in check. But identifying these mystery guards would take him over a decade.
The problem was like trying to spot undercover agents in a crowd. All immune soldier cells look similar on the outside. They carry identification badges—proteins on their surface.
Helper cells wear a badge called CD4, while killer cells wear CD8. In Sakaguchi’s experiment, the protective cells also wore CD4 badges—but they were behaving completely differently from normal helper cells.
His conclusion was revolutionary: there must be different types of cells wearing the same badge.
Finally, in 1995, Sakaguchi announced his discovery to the world. In The Journal of Immunology, he revealed that these special peacekeeping cells wear not just the CD4 badge, but also a second one called CD25. This was their unique signature.
This newly identified cell class was named regulatory T cells—the body’s security guards.
But many scientists remained skeptical. They wanted more proof. That proof would come from an unexpected place: dying mice born during the atomic bomb project.
In Oak Ridge, Tennessee, USA during the 1940s, researchers working on the Manhattan Project were studying what radiation does to living things. Among their laboratory mice, something strange kept happening: male mice were being born with scaly and flaky skin, massively swollen organs, and they died within weeks.
The researchers named this strain “scurfy” and kept breeding them for decades, even though nobody understood what was killing them.
By the 1990s, when genetic tools had become sharper, researchers discovered something chilling: the scurfy mice’s organs were being attacked by their own immune cells. The tissues were being destroyed from the inside. For some reason, the scurfy mutation appeared to cause a rebellion in the immune system—the soldiers had turned on the fortress.
Two researchers who became fascinated by this mystery were Mary Brunkow and Fred Ramsdell. They worked at a biotech company in Washington that developed medicines for autoimmune diseases. They realized these dying mice were trying to tell them something important. If they could understand the molecular mechanism underlying the mice’s disease, they could gain decisive insights into how autoimmune diseases arise in humans.
So they made a crucial decision: they would hunt down the scurfy mutation—find the exact piece of broken DNA causing all this chaos.
Today, this would take a few days. In the 1990s, it was like looking for a needle in a gigantic haystack. The mouse’s X chromosome consists of around 170 million pieces of genetic code. Finding one broken piece in all that information seemed almost impossible.
But Brunkow and Ramsdell were determined detectives. They narrowed the search area down to about 500,000 pieces of code. Then they began the painstaking work of checking every potential gene in that region.
Gene after gene, they searched. Month after month. Year after year.
It was only with the twentieth and final gene that they could shout bingo. After years of dedicated work, they had finally found the scurfy mutation.
The faulty gene was previously unknown. It belonged to a family of genes that act like master switches, turning other genes on and off and controlling how cells develop. Mary Brunkow and Fred Ramsdell named the new gene Foxp3.
While hunting for the scurfy gene, Brunkow and Ramsdell had a hunch. There’s a rare but devastating disease in human boys called IPEX—and like the scurfy mutation, it’s linked to the X chromosome. Boys with IPEX suffer as their immune systems attack their own bodies, often dying in infancy. Could it be the human version of what was killing the scurfy mice?
They found the human version of the Foxp3 gene in a genetic database. Then, helped by pediatricians from around the world, they collected samples from boys affected by IPEX.
When they analyzed the samples, their hunch proved correct: the boys had harmful mutations in the FOXP3 gene.
In 2001, Mary Brunkow and Fred Ramsdell published their bombshell findings in Nature Genetics: mutations in the FOXP3 gene cause both the scurfy mice’s illness and the human disease IPEX. These key findings led to feverish activity in several laboratories around the world.
Scientists began connecting the dots. Could this gene be related to those security guard cells Sakaguchi had discovered?
Two years later, the puzzle came together. Shimon Sakaguchi—and soon other researchers—could convincingly prove that the FOXP3 gene controls the development of regulatory T cells.
Think of FOXP3 as the instruction manual for creating security guards. Without it, the body can’t make these peacekeeping cells. And without peacekeepers, the immune soldiers run wild, attacking everything in sight.
These regulatory T cells prevent other cells from mistakenly attacking the body’s own tissue, which is important for a process called peripheral immune tolerance. They also ensure the immune system calms down after it has eliminated an invader, so it does not continue working at top speed.
The laureates identified the immune system’s security guards, regulatory T cells, thus laying the foundation for a new field of research.
The laureates’ discoveries launched the field of peripheral tolerance, spurring the development of medical treatments for cancer and autoimmune diseases. This may also lead to more successful transplantations. Several of these treatments are now undergoing clinical trials.
Here’s what doctors are now trying:
For cancer patients: Scientists discovered that tumors are clever—they can attract large numbers of these security guard cells to surround themselves like a protective wall. The guards tell the immune system, “Nothing to see here, move along.”
Researchers are therefore trying to find ways to dismantle this wall of regulatory cells, so the immune system can access the tumors and destroy them.
For autoimmune diseases: When someone has diabetes, arthritis, or similar conditions, their immune system is too aggressive. Researchers are instead trying to promote the formation of more regulatory cells to calm things down. In pilot studies, they are giving patients a substance called interleukin-2 that makes regulatory cells thrive.
For transplant patients: Another strategy researchers are testing is to take security guard cells from a patient and multiply them in a laboratory—growing millions more. These are then returned to the patient. In some cases, researchers also modify the cells, putting antibodies on their surface that function like an address label. This allows researchers to send these cellular security guards to a transplanted liver or kidney, for example, and protect the organ from being attacked by the immune system.
The hope is to be able to treat or cure autoimmune diseases, provide more effective cancer treatments and prevent serious complications after stem cell transplants.
“I believe this will encourage immunologists and physicians to apply T regulatory cells to treat various immunological diseases,” said Dr Shimon Sakaguchi upon learning he’d won the Nobel Prize.
One scientist who swam against the tide when everyone else had given up. Two researchers who spent years searching through millions of pieces of genetic code. Together, they discovered something remarkable: your body has its own security force, constantly patrolling to make sure your defence system doesn’t destroy you.
Through their revolutionary discoveries, Mary Brunkow, Fred Ramsdell and Shimon Sakaguchi have provided fundamental knowledge of how the immune system is regulated and kept in check. They have thus conferred the greatest benefit to humankind.
And now, thanks to their work, doctors have new weapons in the fight against diseases that have plagued humanity for generations.
(Edited by Sumavarsha)
