Stockholm- Mary E. Brunkow, Fred Ramsdell, and Dr Shimon Sakaguchi won the Nobel Prize in medicine on Monday for their discoveries concerning peripheral immune tolerance.

Brunkow, 64, is a senior program manager at the Institute for Systems Biology in Seattle. Ramsdell, 64, is a scientific adviser for Sonoma Biotherapeutics in San Francisco. Sakaguchi, 74, is a distinguished professor at the Immunology Frontier Research Centre at Osaka University in Japan.

The immune system has many overlapping systems to detect and fight bacteria, viruses and other bad actors. Key immune warriors, such as T cells, get trained on how to spot bad actors. If some instead go awry in a way that might trigger autoimmune diseases, they're supposed to be eliminated in the thymus - a process called central tolerance.

The Nobel winners unravelled an additional way the body keeps the system in check.

The Nobel Committee said it started with Sakaguchi's discovery in 1995 of a previously unknown T cell subtype now known as regulatory T cells or T-regs.

Then, in 2001, Brunkow and Ramsdell discovered a culprit mutation in a gene named Foxp3, a gene that also plays a role in a rare human autoimmune disease.

The Nobel Committee said two years later, Sakaguchi linked the discoveries to show that the Foxp3 gene controls the development of those T-regs, which in turn act as a security guard to find and curb other forms of T cells that overreact.

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