2025 Nobel Prize in Medicine: regulatory T cells and peripheral immune tolerance

On 6 October 2025, the Nobel Assembly at Karolinska Institutet announced that the Nobel Prize in Physiology or Medicine would go to Mary E. Brunkow (Institute for Systems Biology, Seattle, USA), Fred Ramsdell (Sonoma Biotherapeutics, San Francisco, USA) and Shimon Sakaguchi (Osaka University, Japan) “for their discoveries concerning peripheral immune tolerance”.

What they discovered

Every day the immune system protects us from thousands of microbes, but it must tell what is foreign from what belongs to the body. For a long time, researchers believed this “education” happened only in the thymus, where T cells that could attack our own tissues are removed (central tolerance). The laureates showed that a second layer of control exists.

• 1995: Shimon Sakaguchi described a previously unknown class of T cells, carrying the proteins CD4 and CD25 on their surface, that calm the immune response.
• 2001: Mary Brunkow and Fred Ramsdell showed that a mutation in the Foxp3 gene explains the autoimmune disease of a mouse strain (scurfy), and that mutations in the human FOXP3 gene cause a serious autoimmune disease called IPEX.
• 2003: Sakaguchi proved that the Foxp3 gene governs the development of the cells he had found in 1995, now called regulatory T cells.

Regulatory T cells act as security guards: they monitor other immune cells and make sure the immune system tolerates the body’s own tissues.

Why it matters

According to the Nobel Committee, the discoveries laid the foundation for a new field of research and spurred the development of treatments for cancer and autoimmune diseases. Some tumours attract large numbers of regulatory T cells that shield them from the immune system, and researchers are looking for ways to remove this barrier. In autoimmune diseases they are trying the opposite: increasing regulatory T cells, for example with interleukin-2 (in pilot studies) or by multiplying a patient’s own cells in the laboratory and giving them back. Similar approaches are being studied to protect transplanted organs from rejection.

What it means for patients now

The prize rewards basic research. Treatments based on regulatory T cells are in clinical trials, not in routine care, and it is not yet known which of them will prove safe and effective, or for which diseases. If you or someone close to you has an autoimmune disease or cancer, or is waiting for a transplant, you can ask your doctor whether a suitable clinical trial exists.