“Testing in mice suggests that rejuvenating T cells could make vaccines and some cancer therapies more effective.
A twice-weekly cocktail of three messenger RNAs can rejuvenate the weary immune systems of aged mice and boost responses to vaccination and cancer treatments, a study has found.
The treatment provides a needed boost to immune cells called T cells, which coordinate immune responses and kill infected cells. As people age, their ability to produce T cells wanes, and the ones they have become less effective.
T-cell ageing helps to explain why vaccines are sometimes less effective in older people than in young adults, and why cancer treatments that unleash the immune system against tumours don’t work as well in older adults, says María Mittelbrunn, an immunologist at the Spanish National Research Council in Madrid. Flagging T-cell immunity is also linked to the chronic inflammation associated with many age-related diseases, including some forms of cardiovascular disease.
How to make an old immune system young again
“T cells, in particular, are one of the cell types that change the most during ageing,” says Mittelbrunn, who was not involved in the study. “To rejuvenate them could have immense consequences.”
The work was reported in Nature and at the American Society of Hematology annual meeting in Orlando, Florida.
Targeting T cells
T cells are produced in the bone marrow and then travel to a tiny gland called the thymus to mature. In the thymus, they learn to recognize and respond to pathogens such as bacteria or viruses. They also learn not to attack the body’s own healthy cells.
But the thymus degrades with age: it begins to shrink and is gradually replaced by fatty tissue. Attempts to reverse this using hormone treatments and other drugs have not worked, says Mirco Friedrich, a haematologist and oncologist at the German Cancer Research Center in Heidelberg, and first author of the study.
So, Friedrich and his colleagues decided to take a different approach: rather than treating the thymus directly, they targeted T cells by delivering an experimental therapy to the liver. “Most T cells are in the blood,” Friedrich says. “And the liver receives the body’s whole blood volume.”
The team began by characterizing the effects of ageing on T cells in mice, cataloguing differences in gene activity and molecular signalling pathways from shortly after birth until the animals were old and frail, at about 20 months of age.
The researchers then selected three proteins that seemed to play key parts in T-cell ageing. They encased the mRNA that encodes these proteins into fatty particles that tend to accumulate in the liver, and injected the particles into mice that were about 16 months old, roughly the equivalent of a human in their late fifties or early sixties.
Compared with untreated mice, the treated mice produced more T cells and were more responsive to vaccination and to therapies that stimulate T-cell responses against cancer. Most of the effects of treatment waned once the injections stopped.
Special delivery
Many more studies are needed before the treatment could be tested in humans, says Friedrich. But the three proteins that the team targeted are thought to have similar roles in people, he adds.
The results are promising, says Michelle Linterman, an immunologist at the Malaghan Institute of Medical Research in Wellington, and rejuvenating T cells in the liver is a fresh approach to an important problem.
The study supports a growing appreciation of how the immune system can be restored, she adds. “T-cell ageing is not a fixed process — it is something that is modifiable,” Linterman says. “We can think about changing T-cell biology in a way that actually enables better health in the later years of life.””
1. Nature 649, 276 (2026) Heidi Ledford
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