The 2025 Nobel Prize in Medicine was awarded to Professor Shimon Sakaguchi, Professor Mary E. Brunkow, and Dr. Fred Ramsdell for their groundbreaking discoveries about regulatory T cells and the concept of immune tolerance. Their work has reshaped our understanding of how the immune system maintains balance—defending against threats while avoiding attacks on the body itself.
Dr. Idit Lahover-Rot, director of the Allergy and Clinical Immunology Unit at Rambam Health Care Campus, is an expert in understanding how the immune system maintains tolerance—the ability to distinguish between harmful invaders and the body’s own tissues. This delicate balance is crucial for preventing and treating complex diseases like autoimmune disorders, allergies, and transplant rejection.
“Before we talk about tolerance, we need to understand how the immune system works,” says Dr. Lahover-Rot. She explains that the immune system consists of several branches and cell types, each with a distinct role, yet all working in harmony.
The primitive immune system, known as the innate immune system, is activated in a less selective manner. In contrast, the more advanced and sophisticated adaptive immune system involves multiple cell types, primarily T and B lymphocytes.
“B cells produce and secrete antibodies,” explains Dr. Lahover-Rot. “Their role is to bind to pathogens and tag them for recognition by other components of the immune system, which then work to neutralize the threat. There are countless types of these markers, each with subtle differences.”
T cells—including regulatory T cells—are part of the acquired immune system, which identifies specific threats and retains memory of them. This is where immune tolerance plays a critical role. “Both antibodies and T cells are initially generated in a non-specific manner,” explains Dr. Lahover-Rot. “Their mechanisms undergo training and filtering to ensure they respond appropriately. In infants, these cells are produced by the thymus gland, and later by the bone marrow.”
“Through training and filtering, we can determine which antibodies are specific to pathogens and which ones might mistakenly recognize the body’s own cells,” she explains. “When the immune system detects a marker, it initiates an attack. If something binds to the body’s own cells, the immune system may perceive it as a threat and respond aggressively. The purpose of filtering is to prevent such misguided attacks and maintain immune tolerance.”
However, when the filtering mechanism fails, antibodies may bind to the body’s own cells, prompting the immune system to attack itself—a phenomenon known as autoimmune disease. This is where the scientists’ discovery becomes crucial: additional mechanisms in the bloodstream, beyond the organs, are designed to intercept and neutralize antibodies or proteins that could harm the body. In each induvial, the immune system must learn what to ignore and when to respond. Collectively, these processes are known as immune tolerance.
Nevertheless, we are constantly exposed to harmless substances such as food, pollen, and environmental particles. The immune tolerance mechanism must correctly identify these as safe. When this system fails, the immune response mistakenly treats them as threats—leading to the development of allergies.
Although immune tolerance has been studied for decades, only in recent years have we begun to truly understand how the immune system regulates itself. The Nobel Prize-winning scientists uncovered a key mechanism involving multiple types of T cells that help modulate immune activity. These cells play a crucial role in suppressing unwanted immune responses and fine-tuning the system when a response is necessary. Even when the immune system targets a harmful pathogen, it’s essential that the reaction remains controlled. That’s why regulatory mechanisms are needed—to limit or even prevent an immune response when it’s not required.
Secret of Regulatory Cells
The scientists’ discovery has profound implications for practical medicine. “We now have treatments for many types of diseases,” says Dr. Lahover-Rot. “Some are biological therapies that target substances secreted by T cells, specifically by suppressing cytokines—signaling proteins that drive inflammation. Without the identification of these regulatory systems, the development of such treatments, which form the foundation of autoimmune disease management, would have been impossible.”
This new understanding of the immune system has direct implications for the field of organ transplantation. When a new organ is introduced into the body, the immune system often identifies its cells as foreign and attacks them. “We’ve known about this for decades,” says Dr. Lahover-Rot, “and many of the new drugs used in transplantation are based on these regulatory mechanisms.”
The immune tolerance mechanism also plays a critical role in cancer treatment. Many modern therapies are designed to regulate the immune system’s activity, harnessing its power to target and destroy tumors. By modulating immune responses—either enhancing them to attack cancer cells or suppressing them to avoid damaging healthy tissue—these treatments have become powerful tools in the fight against cancer.
Currently, scientists are developing combination therapies that integrate multiple treatment strategies. As we uncover more immune mechanisms, we gain the ability to combine them in ways that enhance their effectiveness. This approach is one of the key reasons behind the significant advancements in cancer treatment today.
Over-suppression or uncontrolled activation of the immune system can be dangerous. “Sometimes these mechanisms go awry and need to be treated, regulated, and balanced—but ultimately, their role is to protect the body,” says Dr. Lahover-Rot. “If we were to eliminate or destroy all T cells, we couldn’t survive, as they play a crucial role in regulating immune responses. Even when a response is necessary, it must be kept in check.”
According to Dr. Lahover-Rot, any medical intervention must be approached with caution. “I’m in favor of limiting the number of drugs prescribed to a patient, because each one may disrupt a delicate mechanism within the human body,” she explains. “It’s essential that both dosage and treatment are carefully monitored.”
After decades of research, it’s clear that the journey to understanding the immune system is only just beginning. Despite significant progress, many questions remain unanswered. How does lifestyle influence our immune system, and what causes the delicate balance between attack and defense to become disrupted?
“We know there’s a connection between mind and body, but the mechanism linking them remains less understood,” says Dr. Lahover-Rot. “Ultimately, immune tolerance reminds us that the immune system is not just a weapon—it’s a system of restraint, learning, and balance.”
Based on an article that first appeared on YNet
