Montreal study provides insight into how T lymphocytes work

Research carried out in Montreal is providing a better understanding of how an essential component of the immune system works, which could one day lead to clinical applications in the treatment of problems such as infections or even cancer.

After 10 years of work, Dr. Nathalie Labrecque, now at the Montreal Clinical Research Institute (IRCM), and her team published a study on Thursday in the Journal of Experimental Medicine that partially elucidates the cellular and molecular mechanisms that trigger and regulate the T lymphocyte response.

A better understanding of this system—which behaves differently during acute infection, chronic infection, or autoimmune disease—is crucial to the potential development of more effective therapies.

T lymphocytes are capable of killing cells infected by bacteria or viruses, Dr. Labrecque recalled.

“We feel like we know a lot about the T cell response, how it’s put together in a very efficient and coordinated way, which really allows for an optimal response,” she said. “But in reality, there’s still a lot we don’t know.”

Most of Dr. Labrecque’s work was carried out while her laboratory was located at Maisonneuve-Rosemont Hospital. She moved into the IRCM in Jan. 2024.

In a study published 10 years ago, she and her colleagues focused on a signaling pathway called “Notch,” which has long been known to play an important role in the differentiation of many cells in the body. They demonstrated that Notch is also important for the response of CD8+ T cells.

The new study furthers our understanding of this mechanism by identifying the cells that initiate Notch signaling in the first three days after vaccination or infection. It is this signaling that differentiates CD8+ T cells by teaching them which enemy to attack.

“Before that, they are naive lymphocytes, they do nothing, they are waiting,” said Dr. Labrecque, who conducted this work in close collaboration with Dr. Ivan Maillard of the University of Pennsylvania in Philadelphia. “The antigen to which they will respond must be presented to them by a very specific cell.”

And it is this differentiation that will give rise to “the large army (of immune cells) that will control the infection,” she added.

Once the infection is controlled, Dr. Labrecque said, the majority of this army will die, but a small portion will remain, which will become what are called “memory cells.”

“We also showed that the choice between a cell that is destined to die and a cell that will become a memory cell is controlled by notch,” she explained. 

The study therefore lifts part of the veil on the essential role that notch plays in the broader coordination of the immune response, said Dr. Labrecque.

Notch has been found to be involved in T-cell differentiation in the presence of acute infection, and it is conceivable that notch plays an important role in the response to chronic infection, she added.

“This suggests a central role for the notch signaling pathway in CD8+ T-cell differentiation,” she said. “But it opens the question: what is the role of this signaling pathway in the response to chronic infection or cancer?”

–This report by La Presse Canadienne was translated by CityNews