Researchers investigating how specialized immune cells called killer T cells change over the course of our lives have found that, in older age, these cells are replaced by less effective versions that struggle to fight viral invaders. The world-first discovery improves our understanding of age-related immunity and may lead to improved vaccines and therapies tailored to different age groups.
Killer T cells, otherwise known as CD8+ or cytotoxic T cells, possess special molecular weapons to directly attack and destroy other cells infected by a foreign invader such as a virus. As such, they play a critical role in the immune system.
There have been many studies on the actions of killer T cells, but little is known about how they evolve and function across the lifespan. Now, in a study led by the Peter Doherty Institute for Infection and Immunity (Doherty Institute) and the University of New South Wales Sydney, researchers have examined the difference in killer T cells in newborns, school-aged children, adults, and adults 60 years and over, to understand how age affects our immunity to influenza viruses.
“Based on previous studies, we expected to find that killer T cells in older adults were less effective because they had become exhausted or ‘fallen asleep,’” said Carolien van de Sandt, lead author of the study. “However, to our surprise, the very efficient killer T cells that we detected in children and adults seemed to actually disappear and be replaced with suboptimal cells in older adults. It is almost as if you replace the sword of a Roman soldier with a kitchen knife; they can learn how to use it, but it will never be as efficient as the sword.”
The researchers found that the number of total killer T cells was lowest in newborns, increased in children, and peaked in adulthood. Whereas influenza-virus-specific killer T cells were lowest in newborns and children, peaked in adults and decreased in older adults.
They performed gene expression analysis on cells categorized by age and found that influenza-specific killer T cells in newborns and children were genetically similar to those seen in older adults. But markers associated with maintaining immune control, anti-inflammatory cytokines and controlling T cell differentiation were highly expressed in adult influenza-specific T cells, less pronounced in children and older adults, and absent in newborns.
“One of the most intriguing findings of the study was that these cells, with a lower ability to recognize influenza viruses, displayed gene features closely similar to T cells found in newborns,” van de Sandt said.
The researchers say their world-first discovery contributes greatly to our understanding of how immunity changes over the lifespan and has the potential to advance vaccine development.
“Our findings suggest that if we want to boost killer T cells through vaccination, the timing may play an essential role to maintain these optimal killer T cells into old age,” said Katherine Kedzierska, the study’s corresponding author. “This study is a turning point for the research into aging immunity. It has far-reaching implications and opens up new possibilities for the development of better vaccines and therapies tailored to different age groups.”
The study was published in the journal Nature Immunology.
Source: Doherty Institute