Presented by Professor Olle Kämpe
Member of the Nobel Assembly at Karolinska Institutet
Chair of the Nobel Committee for Physiology or Medicine

Your Majesties, Your Royal Highnesses,
Esteemed Nobel Prize Laureates, Ladies and Gentlemen,

This year’s Nobel Prize in Physiology or Medicine honours discoveries that explain how our immune system is agile, adaptable and skilful in defending us against invading microorganisms – while it usually prevents collateral damage to our own tissues in the process.

Every day, we are in intimate contact with countless viruses, bacteria, fungi and even the occasional parasite. During today’s celebrations, we will undoubtedly expose ourselves to a few more airborne particles than usual – and as we shake a great many more hands, the corresponding risks of contact transmission will increase.

Many microorganisms, however, are masters of disguise. They wear molecular “clothing” that resembles our own, making it a delicate balancing act for the immune system to recognise and eliminate invaders without turning its weapons on the body itself. When this balance fails, autoimmune disease develops. To prevent such friendly fire, certain immune cells undergo a rigorous education in an organ called the thymus – known in Swedish as brässen – located in our chest. It also happens to be a culinary delicacy, so there is a small chance that it may even appear on the menu this evening.

Professor Shimon Sakaguchi became intrigued by a curious observation: newborn mice whose thymus was removed just three days after birth developed severe autoimmune disease. He set out to identify which cells went missing when the thymus was gone. After years of meticulous work, he discovered a subset of cells marked by CD4 and CD25 that prevented autoimmunity.

Around the same time, Drs Brunkow and Ramsdell were investigating a peculiar mouse known as the “scurfy” mouse – so named for its flaky skin and widespread inflammation. This mouse had first appeared, of all places, in a large breeding colony during the Manhattan Project in the 1940s. Only males were affected by autoimmunity, hinting that the gene was located on the X chromosome. Narrowing the culprit down to a small region with twenty genes, Drs Brunkow and Ramsdell embarked on the painstaing task of sequencing one gene after the other. The final gene on the list turned out to be the key: FOXP3.

In 2003, Professor Sakaguchi and others could show that his previously identified cells – now known as regulatory T cells – depend on FOXP3 for their identity and function.

These regulatory T cells keep our immune system in balance, preventing autoimmunity while ensuring that immune responses against infections remain strong – but not excessive. Unfortunately, tumours have learned this lesson too well, often surrounding themselves with regulatory T cells to evade immune attacks.

The discoveries made by this year’s Nobel Prize laureates reveal one of nature’s most elegant balancing mechanisms – how the immune system restrains itself to protect the very body it serves without attacking it. Their work opens up new avenues to treat autoimmune diseases, enhance cancer immunotherapy and promote transplant tolerance.

Drs Brunkow, Ramsdell and Professor Sakaguchi, you have uncovered a fundamental principle of natural peripheral self-tolerance – a mechanism that keeps our immune system powerful yet disciplined. On behalf of the Nobel Assembly at Karolinska Institutet, it is my great privilege to convey to you our warmest congratulations. I now invite you to step forward to receive the Nobel Prize from the hands of His Majesty the King.

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