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. A McGill University–led study has now uncovered a previously unknown ability of T cells that could change our understanding of how long-term immunity develops.

The new findings, published in Nature Immunology, reveal 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 behavior."

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.

"Tumors 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 tumors," said Mandl.