Every day, our powerful immune system defends us from microbes trying to invade our bodies. The task is often complicated by pathogens masquerading as our own cells. So how does the immune system stay effective against viruses and bacteria, while making sure not to accidentally attack our own cells in the process?
The Nobel Prize has been jointly awarded to Shimon Sakaguchi, from Osaka University, Japan, and US researchers Mary Brunkow and Fred Ramsdell, from the Institute for Systems Biology in Seattle and Sonoma Biotherapeutics in San Francisco, respectively, for their fundamental discoveries relating to peripheral immune tolerance. The trio all contributed to fundamental research identifying the immune system’s “security guards”—regulatory T cells which prevent aggressive immune cells from attacking our own body.
“Their discoveries have been decisive for our understanding of how the immune system functions and why we do not all develop serious autoimmune diseases,” says Olle Kämpe, chair of the Nobel Committee.
Going against the grain
When Shimon Sakaguchi made the first key discovery on the topic in 1995, he was going against the grain. At the time, scientists recognized two types of T cells—helper and killer T cells. The commonly accepted model was that the immune system prevented these T cells from turning on the body’s own cells by eliminating rogue T cells in the thymus where they matured—a process dubbed “central tolerance”.
Sakaguchi, on the other hand, showed that there was a secondary layer to the defense. Using mice which had their thymus removed, he performed experiments which showed that injecting immune cells from other mice could prevent autoimmune disease from developing. The conclusion: there was a peripheral system for immune tolerance in action—a new, unknown class of T cells which protected the body by policing the problematic T cells.
A new cell is named
Mary Brunkow and Fred Ramsdell added a key piece to the puzzle in 2001, when they uncovered that the gene Foxp3 was the reason behind a specific mouse strain being especially vulnerable to autoimmune diseases. They also found that the equivalent gene in humans was the culprit behind a serious, heritable autoimmune disease called IPEX.
Two years after their discovery, Sakaguchi was able to link this gene to his earlier work, showing that Foxp3 affects the development of the cells he identified in 1995. The mystery cells were dubbed “regulatory T cells” and copious research has since demonstrated their key role in guarding against autoimmune diseases, by making sure other immune cells aren’t attacking the body’s own organs and tissues and by calming the immune response once a pathogen threat has been neutralized.
The far-reaching impact of their fundamental research
The work of Sakaguchi, Brunkow and Ramsdell—along with that of the numerous other researchers and technicians who aided in the discovery of regulatory T cells—launched an entirely new research field in peripheral immune tolerance. Many scientists have since built on this work to spur the development of treatments for cancer and autoimmune diseases, as well as methods for preventing organs from being rejected after transplantation.
It is a striking example of the importance of disruptive discoveries, and how fundamental research can have far-reaching implications for human health.
Header image: Mary E. Brunkow, Fred Ramsdell, Shimon Sakaguchi. Ill. Niklas Elmehed © Nobel Prize Outreach
