Three Scientists Awarded 2025 Nobel Prize in Medicine for Pioneering Discovery of Regulatory T Cells

STOCKHOLM, October 6, 2025 – The 2025 Nobel Prize in Physiology or Medicine has been awarded to three trailblazing immunologists—Dr. Mary E. Branco, Dr. Fred Ramsdell, and Dr. Shimon Sakaguchi—for their seminal discovery of regulatory T cells (Tregs), a specialized class of white blood cells that act as the immune system’s master brakes. Their collective work has fundamentally reshaped our understanding of how the body maintains immune balance, a breakthrough that has paved the way for revolutionary treatments for autoimmune diseases, cancer, and transplant-related complications.

The Nobel Assembly at the Karolinska Institute announced the award this morning, stating that the laureates’ work “solved a fundamental mystery in immunology: how the immune system peacefully coexists with the body it is designed to protect.”

From Heresy to Established Science: The Discovery of the Immune’s “Peacekeepers”

For decades, immunology was dominated by the concept of “central tolerance,” a process in the thymus that eliminates self-reactive immune cells during their development. However, it was clear this process was not perfect. The critical question remained: how does the body prevent the self-reactive cells that escape to the periphery from launching attacks on healthy tissues?

The laureates provided the answer. In the 1990s and early 2000s, through a series of elegant and complementary experiments, they identified and characterized a distinct population of T cells defined by the expression of the CD25 protein and the master regulator transcription factor Foxp3.

• Dr. Shimon Sakaguchi, then at Kyoto University, provided the first conclusive evidence in the late 1990s, demonstrating that CD4+ T cells expressing CD25 were indispensable for preventing autoimmunity. His work showed that removing these cells from mice caused a devastating multi-organ autoimmune disease, while transferring them back could prevent it.

• Dr. Fred Ramsdell and his team made the crucial link to the FOXP3 gene. They discovered that mutations in this gene were the cause of a fatal human autoimmune disorder called IPEX syndrome, and that Foxp3 was not just a marker but the essential “master switch” required for the development and function of Tregs.

• Dr. Mary E. Branco, a systems biologist, built upon this foundation by mapping the intricate signaling networks and epigenetic controls that govern Treg stability and function. Her work revealed how Tregs can be “tuned” to suppress different types of immune responses in various tissues, from the gut to the brain.

A Paradigm Shift with Profound Clinical Implications

The discovery overturned the previous view of the immune system as a purely aggressive force. Instead, it revealed a dynamic, multi-layered system of checks and balances, with Tregs serving as essential “guardians of immune tolerance.”

This paradigm shift has had a direct and growing impact on medicine:

• Autoimmune Diseases: In conditions like multiple sclerosis, type 1 diabetes, and rheumatoid arthritis, Tregs are often dysfunctional or outnumbered. New therapeutic strategies, including Treg-enhancing drugs and cell therapies that involve extracting a patient’s own Tregs, expanding them in the lab, and reinfusing them, are now in advanced clinical trials to restore immune peace.

• Cancer: Tumors often hijack Tregs, recruiting them to create an immunosuppressive environment that shields the cancer from attack. The laureates’ work has spurred the development of next-generation cancer immunotherapies that selectively deplete or inhibit Tregs within tumors, thereby “releasing the brakes” on the immune system to fight cancer more effectively.

• Organ and Stem Cell Transplants: A primary goal in transplantation is preventing organ rejection without broadly suppressing the entire immune system. Treg therapy is being explored as a way to induce transplant tolerance, potentially allowing patients to reduce or eliminate lifelong use of toxic immunosuppressive drugs.

Global Acclaim for a Foundational Discovery

The scientific community has hailed the award as a long-awaited recognition for a discovery that forms a cornerstone of modern immunology.

“Their work transformed a biological curiosity into a central pillar of immunology,” said a statement from the International Society of Immunology. “It provided the ‘why’ behind decades of clinical observations and has given us a powerful new toolkit to manipulate the immune system for therapeutic good.”

In a joint statement, the laureates expressed their gratitude. Dr. Sakaguchi remarked, “We started with a simple question of how the body maintains self-tolerance. To see this fundamental knowledge now helping patients is the greatest reward imaginable.”

The Nobel Committee concluded that the collaborative work of Branco, Ramsdell, and Sakaguchi is a “brilliant example of how fundamental, curiosity-driven science can unravel the most complex biological systems and ultimately translate into life-changing medical progress for humanity.” Their discovery continues to open new frontiers in the treatment of some of the world’s most challenging diseases.

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