In people past 110, one rare T cell keeps growing instead of fading
Osaka researchers found CD4 cytotoxic T lymphocytes rise from 4 percent to 17.6 percent of circulating T cells across the oldest age brackets. Outside immunologists want function, not just counts.
The Scientist · Science desk
What happened
- A team at the University of Osaka published a paper in Cell Reports titled "CD4 CTLs in supercentenarians: Signs of adaptive expansion in healthy aging," with Kosuke Hashimoto, an associate professor at the University of Osaka, as first author.
- The proportion of CD4 cytotoxic T lymphocytes increased with age, with median percentages of 4%, 9.6%, and 17.6% in the 70-99, 100-109, and 110-and-older groups respectively.
- The authors write that aging of the immune system compromises its ability to defend against external pathogens and eliminate internal abnormal cells such as precancerous or senescent cells, increasing the risk of various diseases.
- T cells are traditionally divided into helper cells that coordinate immune responses and killer cells that destroy infected or cancerous cells; CD4 CTLs are an unusual hybrid able to both recognize threats and destroy dangerous cells.
- CD4 CTLs are an atypical and relatively rare T cell population, exceedingly rare in most people.
Why it matters
A team at the University of Osaka reported in Cell Reports that a rare hybrid immune cell, the CD4 cytotoxic T lymphocyte, takes up a progressively larger share of circulating T cells in the very old, reaching a median of 17.6 percent in people aged 110 and over [6][1]. That cuts against the default model of immune aging as subtraction, in which the system loses its capacity to clear pathogens and abnormal cells such as precancerous or senescent ones [14].
CD4 CTLs sit awkwardly in textbook immunology. T cells are conventionally split into helpers that coordinate a response and killers that destroy infected or malignant cells; CD4 CTLs do both, and they are uncommon in most people [2][3]. The same group flagged them as a hallmark of supercentenarians in 2019 [4]. The new work tries to quantify the trajectory.
The cohort is 28 people: eight aged 70 to 99, ten centenarians, and ten supercentenarians [5]. Median CD4 CTL share of total T cells was 4 percent, 9.6 percent, and 17.6 percent across those brackets [1], a 4.4-fold spread between the youngest and oldest groups [13]. The team ran integrated single-cell profiling combining transcriptome, surface protein, and T cell receptor sequence data [8] on more than 40,000 T cells [9], then applied a machine-learning model to a larger dataset of 1,500 people of all ages, which showed a similar trend [16].
Two details do more work than the percentages. First, participants with higher CD4 CTL levels carried many cellular clones, which the authors read as evidence the cells are responding to something rather than merely accumulating [10]. Second, the cells showed no signs of T cell exhaustion, the loss of killing capacity that usually accompanies chronic stimulation [11]. The authors conclude the population expands and diversifies as an adaptation to persistent antigens, potentially contributing to longevity through cancer suppression [20]. Hashimoto's framing is that immune aging is not simply decline, and that selective expansion of certain T cells suggests continued adaptation even in extreme old age [21].
The obvious limit is n. Ten supercentenarians is thin by any normal standard, though Hashimoto notes Japan's national census counts only about 150 in the country, making ten a substantial fraction [7] - roughly 7 percent of the national total [15]. The other limit is direction of causation. Rahul Sharma, an immunologist at the University of Virginia who was not involved, called the study commendable but said more work is needed, and raised the possibility that the cells are simply adapting to survive in older people without benefiting the host [17]. Alon Monsonego at Ben-Gurion University of the Negev, also uninvolved, said the work is not a breakthrough but could serve as a starting point [18]. Manel Esteller at the Sant Pau Research Institute, who studied María Branyas Morera before her death in 2024 at 117 years and 168 days, said the findings show supercentenarians are enriched in cells that attack threats and probably cancer cells [19].
What to watch: whether anyone identifies what these cells actually target. Hashimoto says the next questions are the specific antigens and the role of CD4 CTLs in younger people, some of whom also carry large numbers [12]. Until a target is named, expansion plus clonality plus absent exhaustion is a strong correlation and nothing more.
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Claim ledger
Ranked by verification strength, evidence, and original report placement.
- [1]
The proportion of CD4 cytotoxic T lymphocytes increased with age, with median percentages of 4%, 9.6%, and 17.6% in the 70-99, 100-109, and 110-and-older groups respectively.
- [2]
T cells are traditionally divided into helper cells that coordinate immune responses and killer cells that destroy infected or cancerous cells; CD4 CTLs are an unusual hybrid able to both recognize threats and destroy dangerous cells.
- [3]
CD4 CTLs are an atypical and relatively rare T cell population, exceedingly rare in most people.
- [4]
In 2019 the same team of genetics researchers found that supercentenarians, people who live beyond age 110, have an unusually high amount of CD4 CTLs; the team describes CD4 CTLs as a hallmark of supercentenarians identified in their previous study.
- [5]
The new study examined 28 people in three age groups: eight people aged 70 through 99, 10 centenarians, and 10 supercentenarians.
- [6]
A team at the University of Osaka published a paper in Cell Reports titled "CD4 CTLs in supercentenarians: Signs of adaptive expansion in healthy aging," with Kosuke Hashimoto, an associate professor at the University of Osaka, as first author.
- [7]
Hashimoto said the sample may seem small but that according to Japan's national census there are only around 150 supercentenarians in the country, "so 10 is a substantial number."
- [8]
The investigators conducted integrated single-cell profiling of T cells, combining transcriptome, surface protein, and TCR sequence data across age groups including rare cohorts of centenarians and supercentenarians.
- [9]
The researchers analyzed more than 40,000 immune system T cells.
- [10]
When CD4 CTLs attack an antigen they clone themselves to target it; the study found that people with higher CD4 CTL levels had many cellular clones, which could explain their increased prevalence and implies the cells are actively fighting harmful cells.
- [11]
The researchers found that these immune cells did not show signs of T cell exhaustion, a reduced ability to kill cells such as cancerous ones or those infected by viruses.
- [12]
Hashimoto hopes future research can explore the cells' specific targets and their role in younger people, some of whom also have large numbers of CD4 CTLs.
- [13]
The median CD4 CTL share in the 110-and-older group is about 4.4 times the median in the 70-99 group.
- [14]
The authors write that aging of the immune system compromises its ability to defend against external pathogens and eliminate internal abnormal cells such as precancerous or senescent cells, increasing the risk of various diseases.
- [15]
Ten supercentenarians is about 7 percent of the roughly 150 supercentenarians Japan's national census counts.
- [16]
The team used a machine-learning model to analyze a larger dataset of 1,500 people of all ages, which showed a similar trend.
- [17]
Rahul Sharma, an immunologist at the University of Virginia who was not involved in the research, called the study "commendable" but said more work is needed to understand the cells' function, adding that it is possible they are adapting to survive in older people without actually positively affecting the body.
- [18]
Alon Monsonego, who researches CD4 CTLs at Ben-Gurion University of the Negev and was not involved with the study, said the research is not a "breakthrough" but could be a jumping-off point for further discoveries.
- [19]
Manel Esteller at the Sant Pau Research Institute in Barcelona, who conducted a detailed study of Maria Branyas Morera, the world's oldest woman before she died in 2024 aged 117 years and 168 days, said Hashimoto's research shows supercentenarians are enriched in immune cells that attack threats to the immune system and probably also cancer cells.
- [20]
The authors say their collective findings suggest that CD4 CTLs expand and diversify as an adaptation to persistent antigens, potentially contributing to longevity through cancer suppression.
- [21]
Hashimoto said "Immune aging is not simply a process of decline" and that the selective expansion of certain T cells suggests that even in extreme old age the immune system may continue to adapt to age-related challenges.
Sources
4 independent publishers whose own reporting we read for this story.
- genengnews.comAbundance of Rare Immune Cell Type in Supercentenarians May Help Maintain Healthy Aging
1 article · August 19, 2026
- nature.comDaily briefing: People older than 100 have more cancer-killing cells
1 article · August 19, 2026
- newscientist.comSupercentenarians have hypervigilant immune systems that fight off cancer
1 article · August 19, 2026
- scientificamerican.comSupercentenarians have a cellular superpower
1 article · August 19, 2026
Topics and entities
Topics
- Longevity Research
- T cell immunology
- Immune Aging and Immunosenescence
Entities
- University of Osaka
- Cell Reports
- María Branyas Morera
- Kosuke Hashimoto
- CD4 Cytotoxic T Lymphocytes