In 2006 immunologist and 2025 Nobel prize winner Shimon Sakaguchi co-wrote an article in Scientific American that now feels prophetic. In the story, entitled “Peacekeepers of the Immune System,” Sakaguchi traced a time line of important studies that led to his discovery of an elusive type of immune cell he called regulatory T cells.
In the 1980s the field had largely dismissed the existence of such a class of cells, but Sakaguchi and other scientists proved that regulatory T cells, or Tregs, are the integral “peacekeepers” that prevent the immune system from overreacting and harming the body itself. That process, known as peripheral immune tolerance, stops the body’s primary defense mechanism from entering self-destruct mode, called autoimmunity.
The experiments Sakaguchi cataloged in Scientific American nearly 20 years ago were recognized last week at the 2025 Nobel award ceremony in Stockholm, where he and immunologists Mary E. Brunkow and Fred Ramsdell shared the prize in physiology or medicine for their discoveries.
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“I didn’t expect it, and of course, I was very much pleased,” Sakaguchi says. “I’m happy to have this honor. But at the same time, I really appreciate the community of scientists who have worked together. The progress of this field is really due to the collective effort of many scientists and immunologists.”
In an exclusive interview, Scientific American caught up with Sakaguchi on October 7 EDT, the day after the award announcement. He discussed the crucial findings that led to the discovery of regulatory T cells and clinical trials that harness these cells to potentially treat chronic infections, cancer and autoimmune diseases.
[An edited transcript of the interview follows.]
What was your journey into looking for cells that suppressed the immune system? What drew you to them?
I was very much interested in autoimmune diseases because our immune system normally defends our cells from invading microbes—viruses and bacteria—but sometimes it’s aggressive and destroys our body cells and causes autoimmune diseases such as rheumatoid arthritis and type 1 diabetes. So the immune system has two aspects: good and bad. What’s the mechanism behind this? If we can understand that mechanism, we may be able to treat autoimmune diseases—or the opposite: make the immune system attack abnormal cells, such as cancer cells, arising in our body.
That was my interest when I was a student in medical school, and then I became a researcher to tackle this conundrum. At that time [in the 1980s], the only available approach to study autoimmunity was the mouse model. I happened to find that newborn mice, if you remove the thymus [an organ in the chest that produces various types of T cells], they spontaneously develop autoimmunelike diseases. And then what was interesting was: if you inoculate the thymus-free mice with normal T cells from nonaffected adult mice, you can prevent disease development—meaning that in the normal collection of T cells in the thymus, there must be some cells that can prevent or suppress disease development. That was the start of my research career.
What convinced you that regulatory T cells existed when others abandoned the theory?
I was convinced that autoimmune diseases, similar to [how they can arise] in humans, can be produced in healthy animals by just manipulating the immune system—removing certain T cells. That was always a very solid phenomenon for me. If other hypotheses or other ideas could explain what we saw, I would follow that concept or idea. I always compared what I believed and what [other theories] showed—which one had better explanatory powers. Our results were not so bad—and were even better—so that was the reason that I continued my research on regulatory T cells.
It is really a key issue in modern immunology: How can we realize or understand why the immune system does not react with ourselves?
In 2006 you wrote an article for Scientific American entitled “Peacekeepers of the Immune System.” How did you come up with the name “peacekeepers” for the cells?
That was coined by my colleague and co-author of that article, Zoltan Fehervari—he’s now an editor of Nature. At that time, we talked about how we can name them and make them more relatable. And then he came up with that idea: “peacekeeper.” It was a really nice name because, later on, we gradually realized that regulatory T cells not only are immunosuppressive but also have various other functions, such as promoting tissue repair. So they are peacekeepers for many things.
You essentially documented in the article how pivotal this work was nearly two decades ago. Did you think back then that your research would be recognized for a Nobel Prize?
Actually, I didn’t. I really hoped that we could have a better understanding of immunological self-tolerance. It’s a long-standing, important question in immunology. Even the 1960 Nobel awards were awarded to Peter Medawar and Frank Macfarlane Burnet, who showed that immune tolerance is acquired, not innate. Well, that’s really interesting, but how does it happen? There have been several theories, including clonal deletion: deleting the dangerous self-reactive clones [of T cells]. They are eliminated when they are immature and being produced in the immune system. But that couldn’t explain how usual autoimmune diseases happen—for example, type 1 diabetes or rheumatoid arthritis. So it is really a key issue in modern immunology: How can we realize or understand why the immune system does not react with ourselves?
Are there any therapies or applications of your work that are close to making it to the clinic?
What is fascinating about regulatory T cells is that they are specialized for immune suppression, and so this means that if you strengthen their functions or increase their numbers, it could be a good way to treat autoimmunity or allergies or various diseases. On the other hand, if you reduce the number of these cells or make their function weaker, then the immune response can be enhanced. So it could be good for cancer immunity. We are pursuing both directions, our team and many others. There are many, many trials underway—at the Nobel announcement, the chairperson told us that more than 200 clinical trials are ongoing now.
Our approach is a bit challenging. For the cancer immunity, we’re looking into how to increase the efficacy of current cancer immunotherapies. For example, current immune checkpoint blockade [a type of therapy that uses lab-made antibodies, or inhibitors, that block signals so the immune response can attack cancer cells] is maybe 20 to 30 percent effective and not curative. So our idea is: regulatory T cells are really abundant in cancer tissue and are suppressing effective antitumor immune responses. How can we remove them in tumor tissue? Antibodies can be designed to remove Tregs. We could combine that with the current immune checkpoint blockade and maybe make the cancer immunotherapy more effective.
If you think about the future, we could develop an oral drug of small molecules that may have a similar effect as the molecular antibodies against Tregs [molecules that are typically delivered intravenously in most trials]. Then we can improve cancer immunotherapy, not only in developed countries but also in developing countries.
You mentioned this could be the basis for cancer treatments. How about infections that suppress the immune system, such as HIV/AIDS?
So increasing immune response could be good in a tumor immunity setting but also for chronic infection. We still don’t know if it would work, but if strengthening the immune response can be achieved by reducing Treg numbers, I think that’s one idea for tackling chronic infections.
What advice would you like to give early-career scientists?
It’s maybe a common one, but really what is important is: if you are interested in something, in science or whatever, then pursue and continue working on that. Your interests may change along the course of your study or through your efforts, but you’ll find something in the landscape. Someday you might realize that now you are doing something different from others that’s more fascinating than what you originally pursued. Nowadays you are expected to do something very, very soon and have a result. But it always takes time to arrive at something important.