Mary Brunkow, Fred Ramsdell, and Shimon Sakaguchi were awarded the 2025 Nobel Prize in Physiology or Medicine on Monday for their collective work in the discovery of specialized immune cells that roam the body and keep potentially harmful immune responses in check—preventing them from attacking the body directly (autoimmune responses) or causing harm with overzealous responses to invaders.
Those specialized cells—regulatory T cells—are now well established as playing a key role in peripheral immune tolerance. That is, a non-central process that allows the immune system to strike a delicate balance between being appropriately responsive and aggressive toward intruding germs or foreign dangers while also not running amok.
Before the trio of prize winners came along, researchers thought that such immune tolerance occurred centrally, in the thymus, the primary lymphoid organ that sits in the center of the chest. There, T cells mature, including into two key types: T helper cells, which go on to trigger immune responses when they recognize foreign dangers; and the aptly named T killer cells, which kill cells, including foreign cells, cancer cells, and cells infected by a virus.
Extra protection
In the thymus, T cells are tested before their release to ensure they won't attack components of the body, causing autoimmune diseases. Thymus cells do this by dangling forbidden targets made from tidbits of the body. If any T cells lock onto such an endogenous target via one of their unique, randomly generated receptors, then it means they have the ability to cause autoimmune responses. As such, they are promptly killed off.
However, researchers had inklings that there were other mechanisms to tone down immune responses, ones outside the thymus. These peripheral systems might help catch rogue T cells that somehow pass the central test but still have the ability to attack the body. For a time in the 1970s. researchers floated the idea of "suppressor T cells," but the field was riddled with inconsistencies and false leads that led many to largely abandon the notion.