Researchers identify a way to accelerate "handbrake" immune cells to remove disease faster

Researchers at WEHI have discovered a mechanism to boost immune cells, allowing them to remove disease and infections more quickly.

T cells are immune cells that help in the fight against disease by identifying and killing disease-causing cells.

T cells are held in check by regulatory T cells, or Treg cells, which prevent them from misbehaving and targeting the body’s healthy organs.

Scientists have now identified a technique to purposely throw Treg cells into overdrive by releasing their “handbrake” grip on regular T cells.

Lifting this restriction might boost T cell response and lead to better cancer and infection therapy choices since patients would gain from faster clearance of harmful cells.

The study was reported in Science Immunology by Dr Charis Teh, Associate Professor Daniel Gray, Simon Preston, and Professor Marc Pellegrini.

At a glance

• T cells were allowed to go into speed and increase the immunological response by removing the regulatory “handbrake.”
• The results provide light on how T cells might be controlled to tackle diseases like cancer and viruses while avoiding autoimmune disorders like multiple sclerosis and diabetes
• Scientists have found a mechanism to boost T cell responses, which might be used to speed up the healing of infections and cancers.

Boosted response

To investigate the significance of an enzyme in the immune response, the researchers inhibited its activity in Treg cells.

Scientists discovered that the enzyme caspase-8 regulated Treg cell survival in a way that was dependent on the immunological environment.

Treg cells were able to survive and proliferate when the enzyme was inhibited in healthy environments. However, blocking caspase-8 in Treg cells through an infection resulted in necroptosis, a kind of cell death.

Inhibiting caspase-8 in Treg cells, according to Associate Professor Daniel Gray, is a vital step in releasing Treg cells’ constraints on T cells.

Releasing this “handbrake” would greatly assist patients fighting certain debilitating conditions, such as chronic infections, as the T cells are then able to work overtime to drive the infection down or away. But there is a risk when too many Treg cells die, as this can lead to autoimmune conditions like diabetes and multiple sclerosis.”

Daniel Gray, Associate Professor, Joint Division Head, Division of Immunology, Walter and Eliza Hall Institute of Medical Research 

Associate Professor Daniel Gray added, “Knowing where the immune response can be supercharged to a level that will boost immunity, but not cause autoimmune disease, will be integral to advancing new immunotherapies in the future. Our research findings bring the scientific field closer to establishing this threshold.”

A therapeutic window

The scientists found that human Treg cells were destroyed more quickly than regular T cells after testing a clinically authorized drug on them. This research found a “therapeutic window” in which Treg cells may be killed while regular T cells were spared.

If we were to target caspase-8 in Treg cells correctly, we could temporarily reduce their suppression on the immune system to enable better defense against certain infections and cancers. Our findings have revealed a new role for this enzyme that could be exploited to fine tune the balance of the immune response to pathogens, cancer, and healthy, normal cells.”

Dr Charis Teh, Division of Immunology, Walter and Eliza Hall Institute of Medical Research