Self-renewing Immune Cells could improve Vaccine Design

An unexpected discovery has led scientists from Cardiff University, St George’s, University of London, Imperial College London and the USA, to believe that a key type of immune cell previously thought to die when end stage has been reached “self-renews” in humans.

“Since the COVID-19 pandemic, T-cells – the immune cells that have a crucial role in killing infected cells and protecting us against infection – have been in the spotlight and it is crucial we continue to learn more about the role they play in long-term immunity, for good or for bad,” said lead author Dr Kristin Ladell, from Cardiff University’s School of Medicine.

“Here, we have clearly shown that a type of T-cell we thought was senescent – that is, aged and deteriorating in function – is in fact self-renewing in humans. The very fact this is happening suggests they have a positive role to play in the long-term maintenance of immunological memory, which is critical for human health.” The findings(1) could also have important implications for vaccine design Dr Ladell added.

Conducted on young and elderly adult volunteers with or without HIV-1 infection, the study used complex methods, including cell tracking in humans, advanced imaging technology and mathematical modelling to determine that CD57+ memory T-cells proliferate and self-renew. The experimental results were also complemented by mathematical modelling performed by Professor Becca Asquith’s team at Imperial College London, providing strong evidence that most CD57+ memory T cells self-renew.

“It was already known that CD57+ memory T-cells become more prevalent with age, usually in response to persistent immune stimulation, for example, in people with certain chronic infections, like HIV-1, or certain types of herpesviruses, like cytomegalovirus,” said Professor Derek Macallan at St George’s, University of London.

“What we wanted to find out was whether these cells were actually multiplying or just accumulating, because they were not dying. Our research suggests they are self-renewing, and as such, it would seem they have an important role in keeping chronic infections at bay.”

The study, also involving scientists at the University of California, Berkeley and at the Bill and Melinda Gates Foundation, was funded by Cancer Research UK, the Medical Research Council, the Wellcome Trust, the European Union and the National Institute of Health.

(1) Published in Cell Reports