Memory T cells in tissues outlast those in blood

Memory T cells are a special type of white blood cell that “remember” past infections and vaccines, helping our bodies to quickly respond if we encounter the same germs again. These cells are found throughout the body: some circulate in the blood, while others settle down as “residents” in tissues like the lungs, intestines and lymphoid organs (such as the spleen and lymph nodes).

Scientists have long known that memory T cells are crucial for lifelong immunity, but previous studies focused mostly on T cells in the blood. To fill the research gap, Bruce Buchholz, a scientist at Lawrence Livermore National Laboratory (LLNL), and collaborating researchers conducted a study to shed light on how long these cells live and persist in different parts of the body, and how aging affects their ability to protect us. Their research is published in Immunity.

The big questions the research team sought to answer were: Do these cells last for years, or are they constantly replaced? Do they lose their protective abilities as we get older? And does where they live in the body make a difference?

Methods for measuring cell age

To tackle these questions, the team analyzed blood and tissue samples from 138 organ donors, ranging in age from 2 to 93 years. Using the isotope measurement capabilities at LLNL’s Center for Accelerator Mass Spectrometry (CAMS), Buchholz was able to analyze the samples by employing a cutting-edge technique called “retrospective radiocarbon birth dating,” which measures tiny amounts of a carbon isotope (carbon-14) in the DNA of cells.

Accelerator mass spectrometry works by accelerating ions to extraordinarily high kinetic energies, allowing researchers to count individual carbon-14 atoms in a sample. This level of precision is crucial for accurately estimating the age of cells, since the amount of carbon-14 in the atmosphere has changed over the past several decades due to nuclear testing and other factors. By comparing the carbon-14 content in T cell DNA to historical atmospheric levels, the researchers could determine how long these immune cells had been alive in different tissues.

Key findings on memory T cells

The measurements reveal that not all immune cells are created equal—with memory T cells living for 1–2 years in most tissues, while those in the spleen can persist for 3–10 years. Tissue-resident memory T cells (TRM cells) were also found to keep their special protective features throughout life, unlike circulating memory T cells in the blood, which show signs of aging and reduced function.

This shows that while circulating memory T cells develop aging markers, TRM cells are shielded from immunosenescence, a process where immune cells become less effective with age. Lastly, both types of memory T cells undergo changes in their DNA (epigenetic changes) as we age, but TRM cells show more gene regulation, helping them adapt and maintain their protective roles.

Implications for vaccines and aging

The discovery that TRM cells remain stable and avoid aging-related decline could help scientists develop better vaccines and treatments for infections, especially in older adults. It also opens new doors to understanding how our immune system adapts to aging, and how we might boost its resilience.