2025 Nobel Prize in Medicine for discovery of T-Cells

Every day, the immune system defends us from thousands of invading microbes. But many pathogens mimic human cells to evade detection, making it vital for the immune system to distinguish between foreign threats and the body’s own tissues. White blood cells called T cells play a crucial part in the body’s immune system by attacking infected or cancerous cells. But in 1995, Sakaguchi and his colleagues discovered a previously unknown subtype of T cells — called regulatory T cells. These rare cells serve as crucial brake on the immune system — suppressing it and preventing it from over-reacting. Bucktrout likens the cells to an elite police force that represent only 1–2% of all T cells, but are highly effective at “keeping everyone in order”. At the site of immune reaction in the body they arrive and “shut the whole thing down”, she says. “They really mop everything up and dampen inflammation very effectively.”
The Nobel Prize in Physiology or Medicine 2025 has been awarded to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for ground-breaking discoveries that explain how the body’s immune system is kept in check to prevent it from attacking its own organs. Mary E. Brunkow (born 1961) earned her Ph.D. from Princeton University, USA, and currently serves as Senior Program Manager at the Institute for Systems Biology in Seattle. Fred Ramsdell (born 1960) received his Ph.D. in 1987 from the University of California, Los Angeles, and is now Scientific Advisor at Sonoma Bio therapeutics; San Francisco. Shimon Sakaguchi (born 1951) obtained his M.D. in 1976 and Ph.D. in 1983 from Kyoto University, Japan, and is Distinguished Professor at the Immunology Frontier Research Centre, Osaka University.
The pioneering work on peripheral immune tolerance revealed how a special class of Immune cells, known as regulatory T cells, act as guardians against autoimmune disease. The laureates’ work answered this long-standing question by uncovering the mechanisms behind peripheral tolerance, the immune system’s ability to avoid self-harm. Shimon Sakaguchi paved the way in 1995 when he challenged the prevailing view that immune tolerance was solely maintained by eliminating harmful immune cells in the thymus, a process called central tolerance. His research showed the immune system was more complex, identifying an entirely new type of immune cell—regulatory T cells—that shield the body from autoimmune disorders.
In 2001, Mary Brunkow and Fred Ramsdell advanced this field through genetic research. While studying a mouse strain prone to autoimmune disease, they discovered a mutation in a gene they named Foxp3.This mutation disabled the immune system’s regulatory controls, leading to severe illness. Crucially, they confirmed that mutations in the human equivalent of Foxp3 cause a rare but serious autoimmune condition known as IPEX syndrome. Two years later, Sakaguchi connected the dots, proving that the Foxp3 gene orchestrates the development of the regulatory T cells he had identified earlier. These cells act as immune monitors, ensuring that defensive responses target genuine threats while tolerating the body’s own tissues.
“Their discoveries have been decisive for our understanding of why we do not all develop serious autoimmune diseases,” said OlleKämpe, chair of the Nobel Committee. Beyond transforming immunology, these findings have opened new frontiers for medical treatments. The concept of peripheral tolerance now underpins emerging therapies for autoimmune diseases, cancer, and organ transplantation. Several Foxp3-based therapies are already in clinical trials, with hopes of improving patient outcomes and enabling more successful transplants.
The 2025 Nobel Prize in Medicine celebrates three scientists whose collaborative breakthroughs have reshaped the fight against immune-related illnesses, offering hope for millions affected by autoimmune and inflammatory diseases worldwide. The trio “have provided fundamental knowledge of how the immune system is regulated”, said Nobel committee member Marie Wahren-Herlenius, a rheumatologist at the Karolinska Institute in Stockholm, at a press conference announcing the prize. Their discoveries help to explain “how we keep our immune system under control so we can fight all imaginable microbes and still avoid autoimmune disease”.
The findings led to the development of a range of therapies for autoimmune diseases that are now in early clinical development, says Samantha Bucktrout, an immunologist at Greywolf Therapeutics in Oxford, UK, who has previously worked with Ramsdell.”If it wasn’t for these initial findings — and all of this whole field that these individuals started — we would never be at this place now where we can talk about cures,” she says. Autoimmune conditions — which include type 1 diabetes, arthritis and multiple sclerosis — affect around one in ten people.
In experiments using a marker for regulatory T cells, Sakaguchi showed that mice lacking these cells developed autoimmune conditions of the thyroid, pancreas and other organs, and that giving the animals a solution containing regulatory T cells stopped disease progression. Scientists had suspected that the immune system contained its own built-in brake for decades, but had not been able to prove it. This discovery allowed researchers to isolate and work on regulatory T cells for the first time, and other research teams began to identify different types of regulatory T cell with different kinds of immune-suppressing properties.
Later, in 2001, Brunkow and Ramsdell discovered a mutation in the gene Foxp3 that caused fatal autoimmune disease in mice. They also showed that mutations in the human equivalent of this gene caused a rare genetic autoimmune disease.”It was really a molecular slog to get to that exact mutation, because it was just a very small genetic alteration that results in quite a profound change in the immune system,” said Brunkow in a telephone interview shortly after the prize announcement. “It takes a bunch of different brains all working on it together.”
In 2003, follow-up studies by Sakaguchi and his colleagues showed that Foxp3 is specifically expressed in regulatory T cells and is required for their development5.The work “really changed our view of a lot of conditions and is still changing our view”, says Anne Pesenacker, an immunologist at University College London. The discovery of regulatory T cells, and the markers to identify them, “has helped us so much to understand autoimmunity”, she says. “We’re starting to look at can we boost this regulation.”
Studies have found that people with some autoimmune disorders, including type 1 diabetes, lupus, rheumatoid arthritis and multiple sclerosis, often have too few regulatory T cells in their blood or ones that do not function properly. And even early experiments on mice showed that there was potential to use regulatory T cells in treatment for such conditions , says Pesenacker.
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