The 2025 Nobel Prize in Physiology or Medicine was awarded to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for their discovery on regulatory T cells, which play a vital role in preventing the immune system from attacking the body. The announcement took place at the Karolinska Institutet in Stockholm on October 6, 2025.
Peripheral immune tolerance is a mechanism that keeps the immune system from turning against the body’s own tissues. This process happens outside the brain and spinal cord, within the peripheral immune system, and is essential for preventing autoimmune diseases, where the immune system mistakenly targets the host.
Shimon Sakaguchi was swimming against the tide in 1995, when he made the first key discovery. At that time, many scientists believed that immune tolerance was solely a result of harmful immune cells being eliminated in the thymus, a process known as central tolerance. However, Sakaguchi revealed that the immune system is much more intricate than that, uncovering a new class of immune cells that help protect the body from autoimmune diseases.
In 2001, Mary Brunkow and Fred Ramsdell made another significant breakthrough by explaining why a particular strain of mice was especially susceptible to autoimmune diseases. They found that these mice had a mutation in a gene they named Foxp3. They also demonstrated that mutations in the human version of this gene lead to a serious autoimmune condition known as IPEX.
Two years after this, Shimon Sakaguchi was able to link these discoveries. He proved that the Foxp3 gene governs the development of the cells he identified in 1995. These cells, now known as regulatory T cells, monitor other immune cells and ensure that our immune system tolerates our own tissues.
