People who live extraordinarily long lives have a secret weapon: killer immune cells.
Called CD4 cytotoxic T lymphocytes, or CD4 CTLs, these white blood cells help coordinate the body’s immune response to infection. But instead of just activating the immune system to fight off attacks, they actually destroy the offending cells, targeting viruses, inflammation and even cancer.
CD4 CTLs are exceedingly rare in most people. Back in 2019 a team of genetics researchers found that supercentenarians, or people who live beyond age 110, have an unusually high amount of these cells. Now researchers from the same team have found that these cells increase and clone themselves after people turn 100—a sign that the CD4 CTLs are actively working to combat harmful cells.
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“Together, these findings suggest that the increase is not simply a passive consequence of aging but may reflect an adaptive response to persistent antigens,” says Kosuke Hashimoto, a biologist at the University of Osaka in Japan and lead author of both studies.
In the new paper, the researchers studied 28 people in three age groups: eight people aged 70 through 99, 10 centenarians and 10 supercentenarians. They analyzed more than 40,000 immune system T cells and found that the proportion of CD4 CTLs increased as people aged, with the highest number found in supercentenarians. They then used a machine-learning model to analyze a larger dataset of 1,500 people of all ages, and it showed a similar trend.
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 be the reason for their increased prevalence—and implies that the cells are actively fighting harmful cells. Previous research shows these cells target inflammation and damage from cellular aging.
The new study is “commendable,” says Rahul Sharma, an immunologist at the University of Virginia, who was not involved in the research, but more work is needed to understand these cells’ function. It’s possible that they are adapting to survive in older people without actually positively affecting the body.
Alon Monsonego, who also researches CD4 CTLs at Ben-Gurion University of the Negev in Israel but was not involved with the study, says the research isn’t a “breakthrough,” yet it could be a jumping-off point for further discoveries.
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.
“By combining sufficiently large single-cell datasets, we may be able to study these rare cells and understand what they are doing before their marked expansion in extreme old age,” he says.
“One thing I find particularly remarkable is that, even after more than a century of life, the immune system may still retain the ability to adapt,” Hashimoto adds.