How immune cells develop and retain memory may work differently than medical scientists previously believed, according to an international team of researchers.
The new work shows that T cells—white blood cells essential to immune function—can respond to the physical properties of their surroundings through a kind of cellular sense of touch.
The researchers published the work in Nature Immunology, altering our understanding of how immune cells develop, and potentially improving scientists’ understanding of how the immune system adapts to the varied physical environments found throughout the human body.
T Cells Explained
The various specialized types of T cells serve crucial roles in the immune system. Some directly fight infections, while others help coordinate the immune response. Scientists have long believed that biochemical signals help shape the memory T cells that persist in tissues following an infection, preserving the body’s ability to respond to previously encountered threats. How these cells migrate and eventually settle into strategic positions throughout the body is a key part of the immune response.
As T cells travel through the body, they continually monitor for signs of pathogens. When a threat is detected, T cells can enter affected tissues and help clear the infection. Once the invaders have been repelled, some T cells remain in the tissue to guard against reinfection. These tissue-resident memory T cells help defend against previously encountered threats but can also play roles in autoimmune disorders and the rejection of transplanted tissue.
Over their lifetimes, T cells can develop into increasingly specialized forms. Naive T cells have not yet encountered the specific antigen they are capable of recognizing. Following activation, they can differentiate into effector T cells that help target a particular threat, with some eventually developing into long-lived memory cells.
Tissues in the Body
Tissues in our bodies vary widely in stiffness, ranging from the very soft adipose tissue that makes up our body fat to the much stiffer skeletal muscle tissue. These differences raise an interesting question: how do T cells remain strong enough to survive the pressures of stiffer tissues while staying soft enough to change shape as they slide through obstacles in our bodies?
For their laboratory experiments, the researchers reproduced typical tissue stiffnesses using specially engineered collagen gels. They then placed human and mouse immune cells into the gels and discovered that T cells were more likely to develop characteristics associated with tissue-resident memory cells in stiffer environments.
Previously, scientists believed biochemical signals were the primary driver of tissue-resident memory T cell development. In their new research, the team found that these cells use touch to sense the mechanical pressure of their surroundings, dictated by tissue stiffness, and adjust their morphology to compensate.
“This is an exciting fundamental finding that challenges the way we think about immune cells,” said lead author Judith Mandl, a professor in McGill University’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.”
Correcting T Cells
While T cells normally function to protect us from illness, they can occasionally create problems of their own. Patients with autoimmune diseases and allergies may see these immune cells begin attacking healthy tissue. Additionally, organ transplant patients typically require immunosuppressant drugs to stop their T cells from rejecting the new organ.
“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.
This new research is an important first step in a new understanding of how immune cells differentiate, which could lead to a new foundational understanding of how to correct undesired immune responses.
The paper, “Mechanosensing by T Cells Promotes a Tissue-Resident Memory Transcriptional Program,” appeared in Nature Immunology on July 3, 2026.
Ryan Whalen covers science and technology for The Debrief. He holds an MA in History and a Master of Library and Information Science with a certificate in Data Science. He can be contacted at ryan@thedebrief.org.