The 2025 Nobel Prize-winning discovery of peripheral immune tolerance and regulatory T cells opens new pathways for treating autoimmune diseases.
In the world of science, the ability to recognize oneself is considered the highest form of intelligence.
The immune system is a sophisticated defense network in our bodies. Every day, countless bacteria and viruses attempt to invade our systems, yet healthy individuals don't easily fall ill because this system works effectively.
However, for many years, immunology faced a major mystery: How do immune cells attack external invaders while sparing our own healthy cells?
The research that solved this mystery earned the 2025 Nobel Prize in Physiology or Medicine. Mary E. Blanco, Fred Ramsdell, and Japan's Shimon Sakaguchi elucidated the mechanism of "peripheral immune tolerance," opening new pathways for developing treatments for autoimmune diseases.
How does our immune system identify and attack enemies? The key lies in lymphocytes called "T cells."
These cells patrol the body, guarding against invaders like bacteria and viruses. When they detect abnormalities, they alert other immune cells.
Activated by alerts from helper T cells, these cells destroy infected cells or abnormal self-cells (such as cancer cells).
How do T cells identify abnormalities? The key lies in complex proteins on T cell surfaces called "T cell receptors." These receptors function like sensors that distinguish normal components derived from our own bodies from foreign substances.
Theoretically, our bodies can produce antigen receptors in over 1,000 trillion different configurations. This incredible diversity enables the detection of subtle differences between normal components and countless foreign substances.
If T cells attack external invaders, why don't they attack our own normal cells? This question has existed since the beginning of immunology.
The 1908 Nobel laureate and "father of immunology" proposed that the immune system avoids attacking itself - a concept he called "horror autotoxicus."
The subsequent discovery of autoimmune diseases, where the immune system attacks normal cells, raised new questions about the mechanisms that prevent self-attack.
This characteristic - where immune cells attack foreign substances but spare the body's own cells - became known as "immune tolerance."
Research on immune tolerance began with an accidental discovery in 1945. Ray David Owen found that twin cattle didn't reject each other's blood even when they had different blood types.
Peter Medawar discovered "active immune tolerance" in mouse skin transplantation experiments.
Medawar and Frank Macfarlane Burnet received the Nobel Prize for "discovery of acquired immunological tolerance."
Jacques Miller discovered the role of the thymus. Removing the thymus from newborn mice resulted in severe immunodeficiency.
Experimental proof emerged that the thymus eliminates self-reactive T cells, but this couldn't fully explain immune tolerance.
Through autoimmune disease research, Sakaguchi discovered "regulatory T cells" (Treg) that suppress immune responses. These cells function as brakes on the immune system, preventing other immune cells from attacking the body's own tissues.
They revealed that the FOXP3 gene plays a crucial role in the development and function of regulatory T cells. Abnormalities in the FOXP3 gene prevent Tregs from functioning properly, leading to severe autoimmune diseases.
How did Sakaguchi and colleagues make their groundbreaking discovery? The core of their work lay in a series of clever experiments designed to elucidate the mechanism by which the immune system distinguishes self from non-self.
In the 1980s, immunologists realized that T cell selection in the thymus (central tolerance) alone couldn't fully explain the complete suppression of autoimmune reactions.
A T cell subset expressing CD25 (IL-2 receptor α-chain) was found to suppress other immune cells. These were named "regulatory T cells."
| Characteristic | Details | Significance |
|---|---|---|
| Surface Markers | CD4+, CD25+ | Identification and isolation indicators |
| Key Transcription Factor | FOXP3 | Essential for Treg development and function |
| Primary Function | Suppression of other immune cells | Prevention of autoimmune reactions |
| Secreted Substances | IL-10, TGF-β, etc. | Inhibitory cytokines |
As understanding of immune tolerance advances, groundbreaking clinical trials are progressing across various fields in 2025. Nature Medicine's annual feature highlights 11 clinical trials likely to impact healthcare this year1 .
| Field | Trial Example | Impact |
|---|---|---|
| Gene Therapy | BEAM-101 (Sickle Cell Disease) | Potential cure for hereditary diseases |
| AI Healthcare | Cervical Cancer Screening Chatbot | Expanded healthcare access |
| Personalized Medicine | Precision Cancer Screening | Improved cancer screening accuracy |
| Nutrition Science | Dietary Intervention | Realization of personalized nutrition guidance |
Efficient research progress requires appropriate tools and methodologies. Experienced researchers utilize fundamental but crucial techniques including hypothesis clarification, experimental planning optimization, and data recording standardization.
Excellent research begins with a clear hypothesis. Instead of vague predictions, formulate specific, testable hypotheses.
Visualizing hypotheses as "provisional figures" is also effective. Drawing anticipated results in advance clarifies necessary experimental conditions and control groups.
Seasoned researchers often conduct main experiments and preliminary investigations simultaneously.
For example, using leftover wells in cell plates for main experiments to test reagent concentrations for future studies saves time.
Lab notebook records can also be streamlined. Instead of handwriting the same things repeatedly, print templates for frequently used protocols and attach them to lab notebooks.
| Tool/Method | Specific Application | Advantage |
|---|---|---|
| Hypothesis Clarification | Specific outcome prediction and verification method setting | Research direction clarification, next experiment planning efficiency |
| Provisional Figures | Visualization of anticipated results | Clarification of necessary experimental conditions, easier consensus building |
| Simultaneous Main & Preliminary Experiments | Preliminary investigation using leftover samples from main experiments | Time savings, research speed improvement |
| Protocol Templates | Standardization of frequently used experimental procedures | Reduced recording burden, error prevention |
Research on immune tolerance has not only deepened our understanding of basic immunology but also opened pathways for developing treatments for various diseases. Therapies using regulatory T cells for autoimmune diseases are already in clinical trials, with applications expected for actual patients in the near future.
Remarkable advances are also occurring in AI drug discovery3 . Efforts are underway to design new drug candidate compounds and improve clinical trial efficiency using machine learning and deep learning.
Federated learning technology enables multiple organizations to collaboratively build AI models without sharing data, dramatically increasing the speed and efficiency of drug discovery research.
Developed by Google DeepMind, AlphaFold3 goes beyond predicting protein 3D structures to predicting interactions between proteins and drug candidate molecules, potentially revolutionizing the drug discovery process.
The fusion of immunology research and AI technology will undoubtedly produce more groundbreaking treatments in the future.
| AI Technology | Application in Drug Discovery | Specific Examples |
|---|---|---|
| Machine Learning | Compound activity prediction, biomarker identification | Analysis of disease-gene associations |
| Deep Learning | Integrated analysis of patient data, disease subtype classification | Prediction of treatment response |
| Generative AI | Design of novel compounds | Generation of molecules binding to target proteins |
| Federated Learning | Collaborative AI model building across multiple organizations | AMED project "DAIIA" |
Our immune system possesses the remarkable ability to distinguish self from non-self. The work of the 2025 Nobel laureates who contributed to elucidating this ability demonstrates the beauty at the core of science. It is a story of life's complexity and humanity's quest to understand it.