How does the immune system work? Scientists seeking the answer share Nobel Prize in Medicine

_{© Nobel Committee}

Studying the intricacies of the immune system led to the Nobel Prize in Medicine for three scientists.

Mary E. Brunkow, PhD, of the Institute for Systems Biology in Seattle, Washington; Fred Ramsdell, PhD, of Sonoma Biotherapeutics in San Francisco, California; and Shimon Sakaguchi, MD, PhD, of Osaka University in Osaka, Japan, shared the prize for “their groundbreaking discoveries concerning peripheral immune tolerance that prevents the immune system from harming the body,” according to the Nobel Assembly at Karolinska Institutet, the Nobel Foundation, Stockholm, Sweden.

The trio identified regulatory T cells, “the immune system’s security guards … which prevent immune cells from attacking our own body,” the Nobel summary said.

Mary Brunkow, PhD,
_{© Ross Colquhoun/Nobel Committee}

“Their discoveries have been decisive for our understanding of how the immune system functions and why we do not all develop serious autoimmune diseases,” Nobel Committee Chair Olle Kämpe said in the institute’s official announcement.

Shimon Sakaguchi, MD, PhD
_{© University of Osaka}

The immune system, in humans and other creatures, is “an evolutionary masterpiece” the differentiates between the body’s own cells and microbes that attempt to invade the body.

Fred Ramsdell, PhD
_{© Sonoma Biotherapeutics}

“So how does the immune system keep track of what to attack and what to protect? Why doesn’t the immune system attack our bodies more frequently?” a Nobel Committee explanation said. “Researchers long believed they knew the answer to these questions: that immune cells mature through a process called central immune tolerance.”

But the immune system was more complex than scientists knew. In 1995,Sakaguchi, working at the Aichi Cancer Center Research Institute in Nagoya, Japan, first made the discovery of a previously unknown class of immune cells that protect the body from autoimmune diseases.

In 2001, Brunkow, and Ramsdell, working at Celltech Chiroscience in Bothell, Washington, followed up with another discovery about a gene mutation, named Foxp3, that made mice vulnerable to autoimmune diseases. The human equivalent of the gene caused the autoimmune disease IPEX.

The Nobel Committee acknowledged their painstaking efforts in light of the technology of the time.

“Today it is possible to map a mouse’s entire genome and find a mutated gene in a few days,” a summary said. “In the 1990s, it was like looking for a needle in a gigantic haystack.”

Sakaguchi then linked the discoveries by showing the Foxp3 gene governed development of the cells he discovered in 1995. Now they are known as regulatory T cells that monitor other immune cells, ensuring the human immune system tolerates its own tissues and preventing other T cells from mistakenly attacking the body’s own tissue.

“The laureates’ discoveries launched the field of peripheral tolerance, spurring the development of medical treatments for cancer and autoimmune diseases,” the announcement said. “This may also lead to more successful transplantations. Several of these treatments are now undergoing clinical trials.”

Now there are many more examples of researchers investigating how regulatory T cells might fight diseases.

“Through their revolutionary discoveries, Mary Brunkow, Fred Ramsdell and Shimon Sakaguchi have provided fundamental knowledge of how the immune system is regulated and kept in check,” the Nobel summary said. “They have thus conferred the greatest benefit to humankind.”