A world-first discovery has revealed special immune cells called ‘killer T cells’ in older adults, directed against influenza viruses, closely resemble those present in newborns and kids, but struggle to acknowledge infected cells – a finding that unlocks the potential for the event of higher vaccines and therapies tailored to different age groups.
Killer T cells (also generally known as CD8+ T cells) play a critical role within the immune system by eliminating virus-infected cells. While much has been studied about these immune cells in adults, little was known about how they evolve and performance across the human lifespan – until now.
In a pioneering research published in Nature Immunology and led by the Peter Doherty Institute for Infection and Immunity (Doherty Institute) and UNSW Sydney, researchers employed cutting-edge technologies to look at killer T cells in numerous age groups – newborns, school-aged children, adults and older adults (60+ years) – to know how age shapes our immunity to influenza viruses.
University of Melbourne’s Dr Carolien van de Sandt, a Senior Research Fellow on the Doherty Institute and first creator of the paper, said the team uncovered unexpected similarities in T cell responses between newborns/children and older adults.
“Based on previous studies, we expected to search out that killer T cells in older adults were less effective because they’d change into exhausted or ‘fallen asleep’,” said Dr van de Sandt.
“Nevertheless, to our surprise, the very efficient killer T cells that we detected in children and adults looked as if it would actually disappear and get replaced with suboptimal cells in older adults. It is sort of as in case you replace the sword of a Roman soldier with a kitchen knife; they’ll learn use it, but it’s going to never be as efficient because the sword.
“Probably the most intriguing findings of the study was that these cells, with a lower ability to acknowledge influenza viruses, displayed gene features closely much like T cells present in newborns.”
University of Melbourne’s Professor Katherine Kedzierska, Head of the Human T cell Laboratory on the Doherty Institute and senior creator on the paper, said this research greatly contributes to our understanding of how immunity changes over a person’s lifespan, and has the potential to significantly advance the sphere of vaccinology.
“Our findings suggest that if we would like to spice up killer T cells through vaccination, the timing may play an important role to take care of these optimal killer T cells into old age,” said Professor Kedzierska.
“This study is a turning point for the research into ageing immunity. It has far-reaching implications and opens up latest possibilities for the event of higher vaccines and therapies tailored to different age groups.”
This work was conducted in collaboration with Associate Professor Fabio Luciani, co-senior creator from UNSW Sydney. Associate Professor Luciani said the study provides invaluable insights into the complexity of killer T cell responses as we age.
Importantly, we utilized latest machine learning methods to reconstruct how these influenza virus-specific killer T cells develop over the lifespan. As individuals grow, killer T cells get stronger and simpler at eliminating infected cells, but they disappear in older adults, where they’re taken over by cells with a lower killing capability.”
Fabio Luciani, Associate Professor and Co-senior Writer, UNSW Sydney
Source:
The Peter Doherty Institute for Infection and Immunity
Journal reference:
van de Sandt, C. E., et al. (2023). Newborn and child-like molecular signatures in older adults stem from TCR shifts across human lifespan. Nature Immunology. doi.org/10.1038/s41590-023-01633-8.