Why Doesn't the Immune System Attack Us? — The Brakes on the Patrol

A Splinter in the Finger

When a wooden splinter gets stuck in your finger, the spot turns red and throbs for a day or two. The first to rush to the scene are cells that swallow and destroy bacteria, cleaning up the germs the splinter carried in.

Among the cells that protect the body, there is another group that steps in afterward. These are cells that recognize the enemy one by one, and they are the protagonists this article will follow. This group travels through the blood all over the body, brushing past the heart, skin, joints, and pancreas every day, but they generally leave the body's own cells alone. In some people, however, this group attacks a specific part of the body, such as the joints or pancreas, for a long time.

The system that restrains this group from attacking the body consists of two layers. One layer is the preliminary filtering where those cells grow, and the other layer is the brakes applied throughout the body to the cells that slip through without being filtered out. The 2025 Nobel Prize in Physiology or Medicine went to three scientists who uncovered that second layer, the brakes applied throughout the body (PMID 41255104). This article follows both layers in turn, looks at what happens when the brakes break down, and examines how far treatments that handle these brakes have come.

Why Cells That Aim at Me Are Born

The body has very many T cells that recognize different partners, and a single T cell usually recognizes only one shape of partner. T cells are white blood cells that check protein fragments caught on the surfaces of other cells and recognize invaders or infected cells. Among the groups mentioned earlier that choose and recognize partners, the one this article follows is the T cell. This article compares T cells to a patrol guarding the body.

The single shape that a single T cell recognizes is called an antigen. An antigen is a target recognized by the immune system, usually a portion of an invader or external substance. The fact that T cells recognize such diverse antigens is both a strength of immunity and its Achilles' heel (PMID 16459069). Making them diverse means T cells that react strongly to my body's proteins are also produced along the way, which is why immunity came to be equipped with a mechanism to weed out such cells (PMID 16459069). The way immune cells acquire those numerous shapes is followed in "What Is an Antibody? — Millions of Keys Cut in Advance, and the Ones That Fit".

A self-antigen is among the protein fragments made by my body that immunity can recognize as a target. There is a name for when the patrol aims at such a self-antigen like an invader. Autoimmunity is when immunity, which protects the body, mistakenly recognizes its own body's cells as enemies and attacks them.

Immune tolerance is a state maintained so that immunity does not react to its own body or harmless substances. This state is not given automatically. The research that won a Nobel Prize was about the side of how immunity learns to tolerate self-antigens, which works in places throughout the body (PMID 41255104). Usually, T cells do not react to self-antigens because tolerance is applied in a double layer (PMID 30262031).

Immunity produces countless T cells, and some among them aim at me. Immune tolerance is the two-layered mechanism that holds onto those cells.

The First Layer, Filtering in the Thymus

T cells grow in the thymus, and only 5% of the cells that start growing there finish growing and leave (PMID 12766760). The thymus is a small organ behind the breastbone and right above the heart, where T cells grow and get filtered. Most of the rest die because they do not receive the signal to survive, and some receive the signal to kill themselves because they react to the body's own proteins (PMID 12766760).

Central tolerance is the process in the thymus that eliminates T cells that react strongly to the body's own proteins in advance, preventing such cells from going out into the body. Among the T cells growing in the thymus, those that react strongly to autoantigens are eliminated in this filtering (PMID 21163636).

The thymus is in the chest, but how does it screen out T cells that react to proteins made only in other organs, such as the stomach or thyroid? Some cells inside the thymus directly make thousands of proteins that are normally produced only in specific organs of the body and show them to the T cells (PMID 21163636). AIRE is a gene that makes cells in the thymus produce even proteins that are originally made only in other organs and show them to T cells.

When AIRE is broken, autoimmunity arises spontaneously in both humans and mice (PMID 21163636). In humans, this becomes a rare genetic disease in which multiple hormone-producing glands are attacked. Which glands are attacked varies from person to person, and type 1 diabetes can appear as one of them (PMID 12595897). This rare disease shows to humans that the filtering is actually at work.

Type 1 diabetes is a form of diabetes in which autoimmunity destroys the beta cells of the pancreas, leaving almost no insulin produced. Beta cells are the cells in the pancreas that make insulin.

B cells are white blood cells that make antibodies, and each single cell makes antibodies for only one target. B cells have a similar filtering process, but this article follows T cells.

The filtering is not perfect. Among the T cells that slip out of the thymus and go out into the body, some are mixed in that can react to self (PMID 30262031). One paper that brings together and organizes multiple studies notes, based on calculations and recent experiments, that eliminating T cells targeting self in the thymus is at best imperfect (PMID 37263823).

The thymus filters out T cells that react strongly to self in advance, but it cannot filter them all out.

The Second Layer, Brakes Throughout the Body

T cells that have left the thymus and can recognize self face several fates in the body. They may be locked in an unresponsive state, pass by without meeting a target, or disappear (PMID 30262031). Peripheral tolerance is the process of holding back T cells outside the thymus so they do not attack the body after leaving the thymus and heading out into various parts of the body.

Regulatory T cells are T cells that suppress other immune cells so they do not react excessively. Regulatory T cells strictly monitor the reactions of self-targeting T cells and B cells throughout the body (PMID 30262031). The thymus is both a place of filtration and a place that produces regulatory T cells (PMID 33537838, PMID 26441966), and some regulatory T cells are newly generated outside the thymus (PMID 38374298). Thus, the two layers are connected to each other.

If the patrol is the T cells, regulatory T cells are the brakes applied to that patrol. A healthy immune system relies not only on the power to eliminate pathogens, but also on precise suppression, namely "the brake" (PMID 41536667).

Metaphors have limits. There is no driver stepping on the pedal in immunity. Regulatory T cells work throughout the body in various ways, such as releasing signaling molecules, altering local metabolism, or making direct contact with other cells to suppress them (PMID 41087343). They also help damaged tissue recover (PMID 36792571), a function that is not captured by the word brake.

Cells that have left the thymus are held back again throughout the body, and regulatory T cells are one of those brakes.

The Experiment That Found the Brake

The idea that there are T cells dedicated to holding the immune system in check was proposed as a hypothesis in the 1970s. However, there was no way to isolate those cells clearly and experiments could not be reproduced, so the hypothesis collapsed in the 1980s (PMID 41655742).

Even after that, a few studies kept the idea alive that cells suppressing immunity exist, and the person who found a marker to isolate those cells in mice was the Japanese scientist Shimon Sakaguchi (PMID 41655742). CD25 is a molecule that sits on the surface of some T cells, which Sakaguchi used as a marker to pick out regulatory T cells. In a 1995 experiment, the researchers removed only the cells with CD25 from mice T cells and transferred the rest into mice that lacked a thymus and therefore had no T cells. All the recipient mice spontaneously developed autoimmune diseases in various places like the thyroid, stomach, pancreas, and joints. If the cells that had been set aside were put back in before it was too late, this disease was prevented depending on the amount put in (PMID 7636184).

Those same mice also reacted more strongly when they received skin grafts from other mice or were injected with unfamiliar proteins (PMID 7636184). In mice, this brake suppressed responses against self as well as responses against non-self. Based on these mouse results, the researchers concluded that a breakdown of this mechanism could be the cause of various autoimmune diseases (PMID 7636184). One review paper evaluates that the marker called CD25 gave a physical reality for the first time to those cells that had long been controversial (PMID 41655742).

Removing regulatory T cells caused autoimmunity to develop spontaneously in multiple organs of mice, and putting them back in stopped it.

The Gene That Makes the Brakes, FOXP3

Mutant mice called scurfy die within 16 to 25 days of birth if male. In these mice, T cells proliferate excessively and infiltrate multiple organs (PMID 11138001). In 2001, American scientists Mary Brunkow and Fred Ramsdell found the broken gene in these mice and revealed that a rare genetic disease in humans also stems from a breakdown in the same gene (PMID 41655742). That gene is conserved in almost identical form in humans as well (PMID 11138001).

FOXP3 is the gene that makes regulatory T cells grow into regulatory T cells and do their job, producing proteins that turn various other genes on and off. In a 2003 mouse experiment, FOXP3 was uniquely turned on in regulatory T cells bearing CD25, and was strictly required for those cells to form. The fatal disease in scurfy mice arose from a lack of regulatory T cells, and transferring regulatory T cells prevented the disease. Forcibly turning on FOXP3 in ordinary T cells gave them the power to suppress other cells (PMID 12612578).

The 2025 Nobel Prize in Physiology or Medicine was awarded to Sakaguchi Shimon, Mary Brunkow, and Fred Ramsdell for "discoveries concerning peripheral immune tolerance" (PMID 41255104). A review paper notes that the discovery of FOXP3 turned a disputed concept into an object that could be repeatedly verified and modified (PMID 41655742).

In mice, without FOXP3, regulatory T cells fail to form, and those mice attack their own bodies without brakes.

A Child Whose Brakes Do Not Work, IPEX Syndrome

A newborn baby boy suffers from diarrhea that does not go away, eczema that spreads across his skin, and diabetes—even though he is an infant. There is a rare disease where these three things happen together in a single baby (PMID 33692972, PMID 33668198, PMID 11137992). IPEX syndrome is a rare genetic disease in which a broken FOXP3 gene prevents regulatory T cells from properly forming or working, causing the immune system to attack various parts of the body, usually beginning shortly after birth. There are also cases that start later or present with unusual features (PMID 33692972). This is the human disease corresponding to the genetic defect found in scurfy mice by Brunkow and Ramsdell (PMID 41655742, PMID 11137993).

Inflammation is a response in which the body summons immune cells, causes the area to swell, and reacts against stimuli such as tissue damage, infection, or substances that have entered from outside the body. In IPEX, this response targets the body's own tissues, such as the gut, skin, thyroid, and pancreas (PMID 18317533). Type 1 diabetes, seen earlier, is one of the symptoms that appears early in babies with IPEX (PMID 33692972).

Because FOXP3 is located on the X chromosome, this disease appears in boys, who have only one X chromosome (PMID 33194927). Even when regulatory T cells are present, they can be unstable and impaired in function, failing to prevent other T cells from multiplying (PMID 33692972).

The gravity of this disease has been described differently across eras. A 2007 review paper noted that these children frequently died within two years of birth (PMID 18317533). A 2024 review paper notes that as more people have come to know the disease and diagnose it earlier, the management of the condition has improved, and doctors now see a wide spectrum ranging from very early, severe organ involvement to moderately recurring symptoms (PMID 37994657). Another 2024 review paper notes that even though transplants have become safer and gene therapy is drawing closer, treating these children remains difficult (PMID 38040040).

Treatments that have been used include immunosuppressive drugs and transplants in which blood-forming stem cells from another person are received and grafted. Both have been helpful, but they have limitations, and their lifelong effects are not yet fully known (PMID 35355253). Gene therapy to insert normal FOXP3 into the child's own cells is still in the research stage (PMID 39475830, PMID 35355253).

Both IPEX and the AIRE-related disease seen earlier are rare. The AIRE-related disease is a condition where filtering in the thymus is broken, whereas IPEX is a condition where the brakes of regulatory T cells are broken (PMID 20309000). The two diseases demonstrate that the two layers of tolerance each operate within the human body.

When a single FOXP3 gene is broken, the brakes do not work properly, and the immune system attacks the gut, skin, and pancreas, often starting when the baby is a newborn.

The Path a T Cell Walks

Let us imagine a T cell that reacts precisely to a single protein made by the beta cells of the pancreas has just begun to grow in the thymus. We apply what we saw earlier to this cell.

Cells inside the thymus make and display thousands of proteins that are normally made only in other organs (PMID 21163636). If this cell encounters its target there and reacts strongly to it, the cell is eliminated from the thymus (PMID 21163636). This is the case where the first layer works.

The screening is imperfect, so cells like this sometimes slip out of the thymus (PMID 37263823). Then this cell is locked in a non-responsive state in the body, passes by without encountering its target, or is destroyed. It is also kept in check by regulatory T cells (PMID 30262031). This is the second layer.

In babies born with a broken FOXP3 gene, that second layer does not properly stand, and in such babies, type 1 diabetes is one of the symptoms that appear early (PMID 33692972). What this scene shows is only where the two layers work. Exactly where a gap forms in this path to start common type 1 diabetes cannot be pinned down to a single spot. Screening in the thymus has drawn renewed attention in type 1 diabetes (PMID 15142520), and common autoimmune diseases are intertwined with multiple genes and environmental factors together (PMID 40852720).

In Common Autoimmune Diseases

It is estimated that 7 to 10% of the world's population suffers from autoimmune diseases (PMID 40852720). Autoimmune diseases are conditions in which the immune system attacks the body's own tissues for a long time, leading to inflammation and tissue damage. Some affect the entire body while others target a single organ, and lupus, rheumatoid arthritis, type 1 diabetes, and multiple sclerosis fall into this category (PMID 40852720).

These diseases share a common framework. There is a genetically susceptible foundation, environmental factors such as infections, diet, changes in the gut microbiome, and hormones can trigger the disease in such individuals, and a breakdown of immune regulation is layered on top. Genes alone do not determine whether the disease begins (PMID 40852720). Subtle malfunctions of the thymus may also be added on top of genetic, hormonal, and environmental factors (PMID 33537838).

Opinions are divided on how much of a role regulatory T cells play here. One review paper reports that at the center of it is a failure of peripheral tolerance maintained by regulatory T cells, and notes that data are emerging showing that even when the number of regulatory T cells in people with autoimmune diseases looks normal, the signals inside the cells are weak, preventing them from doing their job properly (PMID 40852720). In many studies, the regulatory T cells of these individuals were reduced in number, function, or both (PMID 30830965). However, another review paper notes that it is still unclear how much of a role regulatory T cell malfunction plays in common autoimmune diseases (PMID 38374298).

What type 1 diabetes changes in the body is covered in "What Is Diabetes? — The Letter That Never Comes, the Letter That Isn't Read".

Common autoimmune diseases involve a combination of multiple genes, the environment, and gaps in tolerance. How much of a role regulatory T cells play among them is not yet clear.

When the Brakes Are Too Strong

Tumor tissues accumulate many regulatory T cells. These cells suppress the immunity that should attack cancer, and that becomes one of the ways cancer evades immunity (PMID 38424196). Both a shortage of regulatory T cells and their overactivity are involved in various diseases, and the growth of autoimmune diseases and cancer falls under that (PMID 41087343).

Therefore, research directions split into two. In cancer, the aim is to reduce or block regulatory T cells, while in autoimmunity and organ transplantation, the aim is to increase or stabilize them (PMID 41087343). Several treatments to eliminate regulatory T cells in cancer have been developed, but most have not shown large effects, and the risk of immune-related side effects also follows (PMID 39890548). One review paper views methods that more selectively target regulatory T cells inside tumors as next-generation treatment candidates with good efficacy and safety. These are still candidate agents in the research stage (PMID 39890548).

Whether regulatory T cells are lacking or working excessively, they are involved in disease. Regulatory T cells gathered in tumor tissue are one of the ways cancer evades immunity.

How Far Have Treatments That Handle the Brakes Come?

Current treatments for autoimmune diseases usually calm the disease by suppressing the entire immune system. However, that calming is often partial and temporary (PMID 39821376).

Attempts to use regulatory T cells themselves for treatment are still in the research and clinical trial stage. Methods of expanding regulatory T cells outside the body and putting them back in are being tested in clinical trials (PMID 30953162, PMID 37400628), and regulatory T cells engineered to recognize only specific targets are also being studied (PMID 37400628, PMID 39821376). A review paper notes the expectation that such cell therapies could produce longer-lasting and more precisely targeted effects (PMID 39821376).

Things that need to be overcome are also noted. Whether the introduced cells stably maintain their brake properties (PMID 30953162), whether they act in the wrong places, and how long the effect lasts are challenges (PMID 39821376). For people whose regulatory T cells are broken starting from their function, simply increasing their numbers may not be the right approach, and data also conflict on at what stage of the disease they should be used to be most effective (PMID 30830965).

Treatments that increase or engineer regulatory T cells for use are still in the research and trial stage.

Where to Look Next

How much of a part the breakdown of regulatory T cells plays in common autoimmune diseases, and how safely and for how long treatments that handle regulatory T cells work, are questions still under research (PMID 38374298, PMID 39821376).

How the immune system recognizes invaders it sees for the first time can be seen in "How Does the Immune System Tell 'Self' from 'Other'? — Guards at the Gate, and a Patrol That Remembers Faces". How immune cells form so many shapes is followed by "What Is an Antibody? — Millions of Keys Cut in Advance, and the Ones That Fit", and the business of the immune system reacting to harmless pollen or food is followed by "What Is Allergy? — A False Alarm, and Why It Rings More Often". Type 1 diabetes continues in "What Is Diabetes? — The Letter That Never Comes, the Letter That Isn't Read".

Source Papers

• "An education in tolerance: the 2025 Nobel Prize in Physiology or Medicine." (2025) — PMID 41255104 — The 2025 Nobel Prize in Physiology or Medicine (Brunkow, Ramsdell, Sakaguchi, peripheral immune tolerance) and the mechanism by which adaptive immunity learns to tolerate self-antigens.
• "Regulatory T cells from concept to clinic: The 2025 Nobel Prize and its implications for immune-mediated diseases and cancer." (2026) — PMID 41655742 — The suppressor T cell hypothesis of the 1970s and its collapse in the 1980s, Sakaguchi's CD25 (1995), Brunkow and Ramsdell's FOXP3 (2001), and the 2003 proof.
• "[Guardians of Immune Tolerance: Regulatory T Cells]." (2025) — PMID 41536667 — Jointly awarded to Japanese scientist Sakaguchi and American scientists Brunkow and Ramsdell; healthy immunity relies on precise suppression (the "brake").
• "The why and how of thymocyte negative selection." (2006) — PMID 16459069 — The diversity of T cell receptors is both the strength and the Achilles' heel of adaptive immunity, which is why negative selection evolved alongside it.
• "T Lymphocytes and Autoimmunity." (2018) — PMID 30262031 — Central and peripheral tolerance, the anergy, ignorance, or deletion of self-reactive T cells that escape the thymus, and the policing of regulatory T cells.
• "Negative selection--clearing out the bad apples from the T-cell repertoire." (2003) — PMID 12766760 — Only 5% of thymic T cells mature and leave; most die from a lack of survival signals, while some die via negative selection.
• "Aire and T cell development." (2011) — PMID 21163636 — Thymic T cells that react strongly to self-antigens are eliminated; Aire expresses thousands of tissue-specific antigens in the thymus, and defects in Aire lead to human and mouse autoimmunity.
• "Autoimmune regulator: from loss of function to autoimmunity." (2003) — PMID 12595897 — AIRE mutations cause APECED, a genetic disease grouping autoimmune endocrine disorders such as adrenal, parathyroid, and type 1 diabetes.
• "Towards a quantitative theory of tolerance." (2023) — PMID 37263823 — Calculations and recent experiments suggest that the elimination of self-reactive T cells in the thymus is at best incomplete (a theoretical review paper).
• "Positive and Negative Regulatory Mechanisms for Fine-Tuning Cellularity and Functions of Medullary Thymic Epithelial Cells." (2015) — PMID 26441966 — The development of self-tolerant T cells and regulatory T cells in the thymus.
• "The regulation and differentiation of regulatory T cells and their dysfunction in autoimmune diseases." (2024) — PMID 38374298 — Regulatory T cells generated in the periphery, FOXP3 mutations causing IPEX, and the unclear extent to which regulatory T cell dysfunction contributes to common autoimmune diseases.
• "Regulatory T cells in homeostasis and disease: molecular mechanisms and therapeutic potential." (2025) — PMID 41087343 — Various suppressive mechanisms of regulatory T cells (signaling molecules, metabolic regulation, contact inhibition), where both deficiency and overactivation are pathological, leading to opposing strategies of reduction in cancer versus expansion in autoimmunity and transplantation.
• "Principles of regulatory T cell function." (2023) — PMID 36792571 — Regulatory T cells are involved in tissue maintenance, repair, and regeneration beyond autoimmune suppression.
• "Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases." (1995) — PMID 7636184 — Transferring T cells depleted of CD25+ cells into nude mice causes multi-organ autoimmunity, re-introducing them prevents it depending on the dose, and responses to foreign entities are also enhanced.
• "Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse." (2001) — PMID 11138001 — Scurfy males die 16 to 25 days after birth with T cell overproliferation and multi-organ infiltration, caused by the Foxp3 gene, which is also conserved in humans.
• "Foxp3 programs the development and function of CD4+CD25+ regulatory T cells." (2003) — PMID 12612578 — Foxp3 is specifically expressed in and essential for the development of regulatory T cells in mice, scurfy disease is due to regulatory T cell deficiency, transfer rescues them, and forced expression confers suppressive function.
• "The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3." (2001) — PMID 11137993 — Genetic evidence that human FOXP3 mutations cause IPEX.
• "X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy." (2001) — PMID 11137992 — X-linked syndrome of neonatal diabetes, enteropathy, and endocrinopathy is the human counterpart of scurfy, caused by FOXP3 mutations.
• "IPEX Syndrome: Improved Knowledge of Immune Pathogenesis Empowers Diagnosis." (2021) — PMID 33692972 — From early onset to late or atypical symptoms of enteropathy, eczema, and type 1 diabetes, regulatory T cells are unstable and functionally impaired even when present.
• "IPEX Syndrome: Genetics and Treatment Options." (2021) — PMID 33668198 — Autoimmune responses beginning around birth, where supportive care for untreatable diarrhea is crucial for the child.
• "IPEX as a result of mutations in FOXP3." (2007) — PMID 18317533 — Autoimmune enteropathy, dermatitis, thyroiditis, and type 1 diabetes due to regulatory T cell deficiency, frequently resulting in death within the first two years of life.
• "IPEX as a Consequence of Alternatively Spliced FOXP3." (2020) — PMID 33194927 — A single FOXP3 mutation on the X chromosome causes IPEX in males.
• "FOXP3 deficiency, from the mechanisms of the disease to curative strategies." (2024) — PMID 37994657 — Management has improved through increased awareness and early diagnosis, showing a broad spectrum from early severe to intermediate recurrent forms.
• "IPEX syndrome from diagnosis to cure, learning along the way." (2024) — PMID 38040040 — Despite advances, treating IPEX remains difficult, with safer hematopoietic stem cell transplantation and gene therapy on the horizon.
• "Towards gene therapy for IPEX syndrome." (2022) — PMID 35355253 — Immune suppression and allogeneic hematopoietic stem cell transplantation have helped, but have limitations and unknown lifelong effects, driving efforts toward gene therapy.
• "Expanding the spectrum of IPEX: from new clinical findings to novel treatments." (2024) — PMID 39475830 — Exploring the potential of gene therapy introducing normal FOXP3 into peripheral CD4 T cells.
• "Autoimmune polyglandular syndromes." (2010) — PMID 20309000 — APS-1 (AIRE, loss of central tolerance) and IPEX (FOXP3) are rare but feature clear mechanisms that serve as a foundation for understanding more common diseases.
• "Back to central tolerance." (2004) — PMID 15142520 — The importance of central tolerance is re-emphasized through research on APECED and type 1 diabetes.
• "Autoimmune disease: genetic susceptibility, environmental triggers, and immune dysregulation. Where can we develop therapies?" (2025) — PMID 40852720 — Estimated at 7 to 10% of the world's population, involving genetics, environment (infection, diet, microbiome, hormones), and immune regulation breakdown, with the authors' view that the core issue is a failure of peripheral tolerance guarded by regulatory T cells.
• "Thymus and autoimmunity." (2021) — PMID 33537838 — The thymus prevents autoimmunity through negative selection and the generation of regulatory T cells, and subtle thymic dysfunction may compound genetic, hormonal, and environmental factors in polygenic autoimmune diseases.
• "The role of FOXP3+ regulatory T cells in human autoimmune and inflammatory diseases." (2019) — PMID 30830965 — Many studies show decreased regulatory T cell function and numbers; proliferative therapy may not be appropriate for patients with functional deficiencies, and data on administration timing are mixed.
• "Regulatory T cell-mediated immunosuppression orchestrated by cancer: towards an immuno-genomic paradigm for precision medicine." (2024) — PMID 38424196 — The accumulation of regulatory T cells in the tumor microenvironment is a mechanism of anti-tumor immune evasion.
• "CCR8: a promising therapeutic target against tumor-infiltrating regulatory T cells." (2025) — PMID 39890548 — Therapies depleting tumor-infiltrating regulatory T cells mostly show limited efficacy and risks of immune-related adverse events, whereas CCR8-targeted therapy specifically directing tumor regulatory T cells is a next-generation candidate with favorable efficacy and safety.
• "Current advancements in cellular immunotherapy for autoimmune disease." (2025) — PMID 39821376 — Current treatments mostly achieve partial and temporary remission via general immune suppression; preclinical and clinical results of cellular therapies such as regulatory T cells face challenges regarding specificity, off-target effects, and persistence, raising expectations for longer-lasting and more specific therapeutic responses.
• "Treg cells in autoimmunity: from identification to Treg-based therapies." (2019) — PMID 30953162 — Clinical trials using polyclonal regulatory T cells, where cellular stability is a major therapeutic challenge.
• "Regulatory T cells in autoimmune kidney diseases and transplantation." (2023) — PMID 37400628 — Attempts to expand regulatory T cells ex vivo or convert them to be antigen-specific.