A McGill University-led study has uncovered a previously unknown ability of T cells that could change our understanding of how long-term immunity develops.
Scientists have long believed that tissue resident memory T cells - which remain in tissues after an infection has cleared and respond rapidly if the threat returns - are shaped primarily by biochemical signals.
New findings published in Nature Immunology challenge this view, revealing that T cells can sense the stiffness of the tissues around them and use these cues to help determine whether they become long-lived memory cells. Researchers suggest adapting to the greater mechanical forces found in tissues may be necessary for memory T cells to survive long term.
"This is an exciting fundamental finding that challenges the way we think about immune cells," said lead author Judith Mandl, Professor in McGill's Department of Physiology. "It suggests T cells can 'feel' their surroundings and adapt to them, making the physical environment an active force in shaping their behaviour."
The discovery was made through a collaboration involving researchers from McGill's Department of Physiology, the Alan Edwards Centre for Research on Pain, the Department of Bioengineering, the McGill University Health Centre and partner institutions in the Netherlands and the United States.
New avenues for research
The discovery could eventually inform new approaches to treating autoimmune diseases, allergies and transplant rejection, where T cells can mistakenly attack healthy tissue.
The findings may also have implications for cancer research, the authors note.
"Tumours are often dense and physically difficult for immune cells to penetrate. Understanding how T cells adapt to these environments could help researchers design cancer immunotherapies that are better able to reach and attack tumours," said Mandl.
How the discovery was made
To test how T cells respond to their environment, immune cells from humans and mice were placed in engineered collagen gels that replicated tissues of varying stiffness. The stiffer the gel, the more likely the cells were to develop into cells resembling tissue resident memory cells, which are associated with long-term immune protection.
Researchers say their next challenge is identifying the molecular sensor that allows T cells to feel their environment and translate physical force into biological change.
About the study
"Mechanosensing by T cells promotes a tissue-resident memory transcriptional program" by Jérémy Postat and Judith Mandl et al., was published in Nature Immunology.
The study was supported by the Human Frontier Science Program, the Canadian Institutes of Health Research, the Canadian Foundation for Innovation, the Natural Sciences and Engineering Research Council of Canada and the U.S. National Institutes of Health.
