Nobel prize for medicine goes to trio for work on immune tolerance

The 2025 Nobel Prize in Physiology or Medicine honors three outstanding researchers – Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi – for their pivotal role in uncovering a vital type of immune cell that prevents the immune system from attacking the body’s own tissues.

“This research has opened a completely new realm in immunological studies,” asserted Marie Wahren-Herlenius at Sweden’s Karolinska Institute.

T cells, a form of immune cells, are crucial for immunity as they target harmful viruses and bacteria through specific surface receptors. Our body continues to produce new T cells throughout our lifetime.

Occasionally, however, the receptors on these newly formed T cells may mistakenly attach to the body’s own proteins, leading to autoimmune disorders like type 1 diabetes and rheumatoid arthritis.

The body has mechanisms to eliminate self-reactive T cells, primarily through testing in the thymus, a process that was once believed to be the sole means of removing these harmful cells.

In 1995, Sakaguchi from Osaka University conducted studies on mice that highlighted the existence of alternative cells in the bloodstream that serve as protectors against auto-reactive T cells. His findings demonstrated that mice devoid of their thymus post-birth developed autoimmune diseases, yet injections of healthy T cells from other mice prevented this outcome. The cells responsible for this protective effect were identified as CD25 regulatory T cells, noted for a specific protein on their surface.

On another front, Brunkow from the Institute for Systems Biology in Seattle, and Ramsdell, who advises Sonoma Biotherapeutics in San Francisco, were investigating a mouse strain prone to autoimmune disorders. Their collaboration in 2001 led to the discovery of a mutation in a gene on the X chromosome, named Foxp3, within these mice.

Mutations in the Foxp3 gene in humans are linked to a heightened risk of autoimmune diseases, a condition known as IPEX syndrome. By 2003, Sakaguchi had established a connection between these discoveries: the Foxp3 gene is essential for the development of the CD25 regulatory T cells identified by his team. Many in the scientific community were initially skeptical about Sakaguchi’s claims, but the findings from Brunkow and Ramsdell solidified his earlier conclusions.

The identification of regulatory T cells holds promise for improved treatment options across various diseases. For instance, increasing the number of these cells could help manage autoimmune conditions such as type 1 diabetes, while reducing their count might enhance the immune response against tumors. Several clinical trials are currently in progress.

“These discoveries are fundamental to our comprehension of immune system mechanisms and the reasons why not everyone develops serious autoimmune diseases,” stated Olle Kämpe, chair of the Nobel Committee, in a press release.