GoKawiilPeople who live to 110 years and older have large populations of a rare type of immune cell that can kill cancer1, finds a study published today in Cell Reports. It is possible that such cells, called killer T cells, might help people to live to extraordinarily long ages by fighting off cancer — although the authors of the study acknowledge that this has yet to be proved, and so far, they aren’t sure exactly what these cells do.
Supercentenarians — people aged 110 and older — not only enjoy unusually long lives but they also seem to fend off diseases of old age including heart disease, dementia and cancer. Researchers hope that studies of supercentenarians’ immune systems might help them to understand why these rare individuals live such healthy lives, and provide clues to help everyone stay healthy longer.
“Most of immune ageing research has focused on decline,” says co-author Kosuke Hashimoto, a biologist at the University of Osaka, Japan. “Our study suggests that even at extreme old age, the immune system may still selectively adapt.”
Rare cells
The current study builds on a 2019 finding2 by Hashimoto and his colleagues that supercentenarians have relatively large numbers of rare CD4 cytotoxic T lymphocytes (CD4 CTLs). Cytotoxic cells kill other cells. CD4 CTLs typically make up less than 5% of the total population of T cells in the body. They’re not as well studied as other kinds of T cell, but they are commonly detected during viral infections, and there’s increasing evidence that they can kill cancer cells, including lung cancer and melanoma cells. Hashimoto says that his team wanted to find out at what age CD4 CTLs proliferate.
Supercentenarians are challenging to study because not many people live that long, says Hashimoto. In Japan, where his team did the study, there are only about 150 people aged 110 or older, he says. The study enrolled 28 participants, including some relatively young people: eight individuals aged 70–90, ten centenarians (people 100–109 years old) and ten supercentenarians.
As the researchers had previously found, CD4 CTLs were abundant in supercentenarians. But they were also found in large numbers in people aged 100 and older, suggesting that this immune adaptation begins around that age. The younger people had normal abundance of these cells, with CD4 CTLs making up 4% of their total T cells. The proportion was around 10% in centenarians and around 18% in supercentenarians.
And they found that these cells seem to be responding to specific immune threats. Each T cell that the body makes produces a unique receptor, which allows the body to recognize and respond to a wide array of antigen threat signals. When a killer T cell encounters its antigen, it will clone itself, producing a line of identical cells that kill the target. In the study’s centenarians and supercentenarians, the researchers found that single clonal lines made up a large percentage of the total CD4 CTLs. In the sample of one centenarian, for example, 53.8% of the cells were identical to each other. This suggests that their immune systems were leaping into action in response to a particular persistent trigger.
Because the cells were found circulating in the blood, the research team could not determine which tissues they were entering and what they were doing. To get some clues, they examined the receptors found on the most common CD4 killer cell lines. They compared the amino-acid sequences of these cell lines with those in a database of CD4 cell receptors. Around 30 sequences from the study matched those from people with cancer in the database. Matches to people with lung cancer were most frequent, even though none of the people in the study had experienced any kind of cancer during their lives.
Adaptive response