The 2025 medicine Nobel goes to the discovery of regulatory T cells

The Nobel Assembly at Karolinska Institutet awarded the 2025 Nobel Prize in Physiology or Medicine on 6 October to Mary E. Brunkow of the Institute for Systems Biology in Seattle, Fred Ramsdell of Sonoma Biotherapeutics in San Francisco, and Shimon Sakaguchi of Osaka University, "for their discoveries concerning peripheral immune tolerance" [s1]. The 11 million Swedish kronor prize is shared equally [s1].

The citation names a concept most people have never heard of, and the shortest way to explain why it matters is to state the problem it solves.

The problem

The immune system has to attack invading microbes without attacking the body it lives in. Many pathogens have evolved surface features resembling human cells as camouflage [s1]. So the system needs a way to tell self from non-self that is reliable enough to work every day for a lifetime.

The answer the field had settled on by the early 1990s was central tolerance: potentially harmful immune cells are eliminated in the thymus before they ever circulate [s1]. On that account, tolerance is a screening problem solved once, at the factory.

The first discovery, against the consensus

In 1995 Sakaguchi showed the system was more complex than that, identifying a previously unknown class of immune cells that protect the body from autoimmune disease [s1]. The Nobel Assembly notes that he was working against the prevailing view at the time, when many researchers were convinced tolerance came from thymic deletion alone [s1].

The 1995 paper, in the Journal of Immunology, framed the finding as immunologic self-tolerance maintained by activated T cells expressing the interleukin-2 receptor alpha chain, CD25 [s2]. That surface marker is what made the cells findable — a subset defined by something you could stain for, rather than an inferred activity.

The second discovery, from a mouse nobody could explain

In 2001 Brunkow and Ramsdell explained why a particular mouse strain was so vulnerable to autoimmune disease [s1]. The animals — the scurfy strain — carried a mutation in a gene the team named Foxp3 [s1]. Their paper described disruption of a new forkhead/winged-helix protein, scurfin, as the cause of the fatal lymphoproliferative disorder those mice develop [s3].

They also showed that mutations in the human equivalent of the gene cause a serious autoimmune disease, IPEX [s1].

That is the step that converted a mouse genetics result into a human one. A gene whose loss kills mice with runaway immune activation, and whose loss in people causes a severe inherited autoimmune syndrome, is doing something load-bearing.

The link, two years later

In 2003 Sakaguchi connected the two discoveries, proving that Foxp3 governs the development of the cells he had identified in 1995 [s1]. The paper, in Science, reported control of regulatory T cell development by the transcription factor Foxp3 [s4].

With that, the pieces fit: a distinct cell population, a master transcription factor that specifies it, and a human disease that results when the factor is broken. These cells — now called regulatory T cells — monitor other immune cells and ensure the system tolerates the body's own tissues [s1]. The Nobel Assembly describes them as the immune system's "security guards" [s1].

Why it took thirty years to be recognised

The gap between 1995 and 2025 is instructive about how this kind of biology gets validated. A claim that a specialised cell type actively suppresses autoimmunity was, in 1995, an assertion about a cell population defined by a marker. It became a mechanism when the transcription factor was found, and it became medicine when the human disease was connected to it.

Olle Kämpe, chair of the Nobel Committee, is quoted in the press release saying the discoveries "have been decisive for our understanding of how the immune system functions" [s1].

What it enabled, and what it has not yet

The Nobel Assembly states that the laureates' discoveries launched the field of peripheral tolerance and spurred development of medical treatments for cancer and autoimmune diseases, and may lead to more successful transplantations [s1]. It adds that several of these treatments are now undergoing clinical trials [s1].

That last clause is the honest boundary. The logic is symmetrical and appealing in both directions — suppress regulatory T cells to unleash an anti-tumour response, expand or transfer them to calm autoimmunity or protect a transplant. But "undergoing clinical trials" is not "approved and working." The prize recognises a discovery whose therapeutic consequences are still being established, and the citation is careful to say so.

The people

Mary E. Brunkow, born 1961, holds a PhD from Princeton University and is a senior program manager at the Institute for Systems Biology in Seattle [s1]. Fred Ramsdell, born 1960, received his PhD in 1987 from the University of California, Los Angeles, and is a scientific adviser at Sonoma Biotherapeutics [s1]. Shimon Sakaguchi, born 1951, holds an MD from 1976 and a PhD from 1983, both from Kyoto University, and is a distinguished professor at the Immunology Frontier Research Center at Osaka University [s1].

The Nobel Assembly consists of 50 professors at Karolinska Institutet, and its Nobel Committee evaluates nominations [s1].

Sources

• The Nobel Prize in Physiology or Medicine 2025 – Press release — The Nobel Assembly at Karolinska Institutet, 6 October 2025
• Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25) — The Journal of Immunology, 1995
• Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse — Nature Genetics, 2001
• Control of regulatory T cell development by the transcription factor Foxp3 — Science, 2003