Regulatory T cells: the 2025 Nobel prize in physiology or medicine

Fred Ramsdell, and Shimon Sakaguchi 'for their discoveries concerning peripheral immune tolerance'.The award honours the discovery of a unique subset of immune cells -Regulatory T cells (Tregs) -which differ fundamentally from most immune cells that typically promote inflammation.In contrast, Tregs suppress immune activation, maintain immune homeostasis, and prevent immunemediated tissue destruction.Without Tregs, the immune system fails to regulate itself, leading to catastrophic multiorgan autoimmunity.Although Tregs are now well-established, their discovery followed a long and challenging path.In the 1970s, the concept of 'suppressor T cells' was proposed and linked to the I-J locus, which was initially believed to encode a key regulatory molecule, present in Major Histocompatibility Complex (MHC) a part of H-2 complex (1).But in 1983, the I-J locus was shown not to exist in suppressive T cells, casting doubt on the entire suppressor T-cell field (2).Between 1982 and 1990, research teams including Shimon Sakaguchi, Don Mason, and Fiona Powrie continued to investigate T-cell subsets with suppressive activity in rodent models.Their work identified T-cell populations capable of preventing autoimmune disease and wasting syndromes in mice and rats (3, 4), keeping the field alive despite the skepticism of many researchers.