Australian discovery of change in ‘killer T cells’ could help fight against influenza

Research led by Dr Carolien van de Sandt, a senior research fellow at the Doherty Institute and 2023 Claude Hannoun Prize, and UNSW Sydney shows that cells are replaced as we get older by ones less able to read threat from infections.

A world-first discovery from Australian researchers unlocks the potential for the development of better vaccines and therapies against influenza viruses tailored to different age groups.

The paper, published in Nature Immunology on Tuesday, has revealed special immune cells called “killer T cells” in older adults closely resemble those found in newborns and children.

Killer T cells play a critical role in the immune system by eliminating virus-infected cells and establishing long-term immunological memory. The research, led by the Doherty Institute and UNSW Sydney, examined these cells in four different age groups: newborns, school-aged children, adults and older adults aged over 60 years of age.

The lead author, Dr Carolien van de Sandt, a senior research fellow at the Doherty Institute, said it was previously believed that people maintain the same killer T cells throughout their whole life but that these cells became less effective as they became exhausted or “fell asleep” as people become older.

However, what the researchers found was that the effective cells found in children and adults actually disappear in the elderly, to be replaced by new cells, which are less able to recognise virus-infected cells.

And these new cells displayed gene profiles closely similar to T cells found in newborns, which still need to learn how to recognise influenza viruses, van de Sandt said.

“They have the capacity to respond very well,” she said. “They look very similar on the inside like they’re young cells, but the outside is different and doesn’t recognise [virus-infected cells] anymore. It’s almost like they need reading glasses.”

Van de Sandt compares the new, less effective cells to having sword swapped with a kitchen knife: “You can learn how to use it, but it will never be as effective.”

Prof Katherine Kedzierska of the University of Melbourne, who is head of the human T cell laboratory at the Doherty Institute and a senior author on the paper, said the research will help understand how immunity changes over an individual’s lifespan, which has the potential to significantly advance the science of vaccination.

“This study is a turning point for the research into ageing immunity. It has far-reaching implications and opens up new possibilities for the development of better vaccines and therapies tailored to different age groups,” Kedzierska said.

This work was conducted in collaboration with Prof Fabio Luciani, co-senior author from UNSW Sydney, said new machine learning methods were used to reconstruct how the influenza virus-specific killer T-cells develop over the lifespan.

“As individuals grow, killer T cells get stronger and more effective at eliminating infected cells, but they disappear in older adults, where they are taken over by cells with a lower killing capacity,” Luciani said.

Prof James Trauer, the head of epidemiological modelling at Monash University, who was not involved in the research, said “immunity to many pathogens - including influenza and Covid - is clearly strongly influenced by factors other than what we can measure through standard blood tests (ie serology)”.

“So understanding cellular immunological processes through studies like these is very important,” Trauer said.