A new fluorescent imaging strategy allows researchers to track T-cells and further understand their dynamics in vivo, giving them insight into what happens when these immune cells attack myelin in a mouse model of multiple sclerosis (MS).
The new technology was reported in the study, “A timer for analyzing temporally dynamic changes in transcription during differentiation in vivo,” published in the Journal of Cell Biology.
T-cells are key players in the immune system, vital in the fight against infections, but a subset of these cells are also believed to play an important role in the myelin-damage process in MS.
In response to infection, T-cells are activated. The cells have a receptor at their surface, called a T-cell receptor, that acts as a surveillance signal and, upon detection of a pathogen, triggers a signaling cascade that culminates with T-cells’ “transformation” into a specific state capable of killing the infectious agent.
This transformation process, called differentiation, is very dynamic, making it difficult to track and analyze in vivo.
A team of researchers at the Imperial College London in the U.K., have now developed a new tool they call “Timer of cell kinetics and activity,” or, “Tocky,” after the Japanese word for time, that allows them to follow T-cell differentiation in vivo.
“This new method allows us to identify and analyse the activities of cells inside the body in a systemic manner, giving us a better understanding of how they work over time,” Masahiro Ono, MD, PhD, the study lead author’s and a principal investigator at the department of life sciences at Imperial College London, said in a press release.
Specifically, the researchers attached a fluorescent protein called Timer to a target gene of the T-cell’s receptor. The Timer protein changes color from blue to red when T-cells are activated, and enables researchers to follow the cells’ differentiation, and identify the molecular pathways that accompany this process.
“Using this new technology, we were able to understand and correlate events with the passage of time following T cell receptor signalling in vivo. This has been previously very difficult to do,” Ono said.
When they deployed this system in a mouse model for MS, called an experimental autoimmune encephalomyelitis model, researchers identified the tissue-infiltrating T-cells that attack myelin in the central nervous system (CNS).
Moreover, they saw that the CNS-infiltrating T-cells are unique in their activities across the brain and spinal cord, and are continuously reactivated. These results show the specific pattern of T-cells in MS, which could help scientists further understand the disease, and potentially come up with new ways to treat it in the future.
In addition, the new tool could be used to better understand how immunotherapies used to treat cancer work and how the immune system responds to these therapies.
“What I hope is that by improving our understanding of how cells work systemically in the body, we can create a better and even more tailored method to manipulate our immune system for human health benefits,” Ono said.
Researchers are now trying to adapt the Timer protein for other immune cells so they can gain more understanding on the different components of the immune system response.
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