When the immune system ages, it loses its top team players
How does the body respond to influenza over time and what implications does this have as you age? Dr Carolien van de Sandt Senior Research Fellow and Professor Katherine Kedzierska, Laboratory Head (Dept of Microbiology & Immunology at the Doherty Institute) answer this in their latest research. Here's what they had to say.
The immune system, particularly Killer T cells (also known as CD8+ T cells), plays a vital role in defending the body against viruses such as influenza. A key characteristic of these cells is their ability to remember the viruses they have eliminated, allowing them to respond faster and more strongly when you are reinfected with the same virus.
We investigated how our immune system evolves throughout the human lifespan and how these changes influence our ability to combat viruses. We have previously shown that Killer T cells targeting the influenza virus are less effective in older individuals compared to those in younger individuals. However, until now, the cause of this difference has remained unknown.
In our recent publication in eBioMedicine, we followed a group of adults and older individuals over a period of seven to 12 years to see how their Killer T cell populations change over time. We were particularly interested in whether we could detect the same Killer T cells across multiple time points.
We found that both the highly functional Killer T cells in adults and the less functional Killer T cells in older individuals are long-lived, which means we could detect the same cell at multiple timepoints in the same donor.
Additionally, in adults, we observed that when the highly functional population decreases, other highly functional cells that resemble them take over. In other words, adults have a spare population of Killer T cells of the same quality.
In contrast, older individuals lack this reserve. Once the highly functional populations decrease and eventually disappear, they are replaced by less functional Killer T cells. As these too diminish over time, they can only be replaced by similarly low-functioning Killer T cells, leading to a progressive decline in immune effectiveness.
Think of your influenza-specific Killer T cells as runners in a relay race. At first, the team consists of top athletes who are fast, strong, and capable of covering long distances before handing off the baton. For the initial few handovers, each new runner is as fit and effective as the last. Eventually, all the elite runners take turns and the baton is passed to less experienced amateurs. They try their best, but in general are slower and cannot run as far, making it harder for the team to maintain the same pace.
Our findings help explain why older individuals are at higher risk for severe influenza infections. Their Killer T cells that normally play an important role in stopping an infection are now not only lower in numbers and less efficient (shown in our previous study), but our current study shows that their backup cells are also of reduced quality.
This means that it is especially important for older individuals to get vaccinated at the start of the influenza season to boost other parts of their immune system, which will help protect them against circulating influenza viruses.
This article was originally published by the Doherty Institute on 23 April 2025.