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Key type of immune cell ‘self-renews’ in humans, new study finds

Published: 16 December 2020

Professor Derek Macallan, author on the study, at St George's Professor Derek Macallan, author on the study, at St George's

A team of scientists has shown that a key type of immune cell “self-renews” in humans.

It was previously thought that this specific type of “senescent” killer immune cell, known as the CD57+ memory T-cell, had reached “end-stage” and would die following one more stint at helping people fight off – or live with – certain infections.

The latest discovery suggests these cells could play a much bigger part than previously thought in lifetime immune memory, and the finding could also have important implications for vaccine design.

The research, a collaboration between St George’s, University of London, Cardiff University, Imperial College London, and scientists in the USA, is published today in the journal Cell Reports.

“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.”

In this study, the researchers 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 in vivo.

They tracked the cells using heavy water containing the stable isotope deuterium in young and elderly adult volunteers, with or without HIV-1 infection. As deuterium is incorporated into cells when they divide into daughter cells, the fraction of deuterium-positive cells correlates with the self-renewal of the cells of interest.

The experimental results were 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 and thereby contribute to long-term immunological memory.

“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, author on the study, 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.”

By further understanding how immunological memory is maintained, this could help researchers to uncover how to develop vaccines that provide long-lasting protection – something that will be crucial in the current pandemic and beyond.

The study also involved scientists based at the University of California, Berkeley, and at the Bill and Melinda Gates Foundation.

The work was funded by Cancer Research UK, the Medical Research Council, the Wellcome Trust, the European Union and the National Institute of Health.

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