In work, partly funded by JDRF, researchers in the UK and Australia have shown that ‘training’ immune cells with a form of insulin can help the immune system to delete immune cells that attack beta cells.
Why did they do this research?
The immune system has a quality control stage, where it checks that all of its immune cells are working correctly, before releasing them into the bloodstream. One of the factors that leads to type 1 diabetes is that the quality control stage doesn’t pick up on T cells – a type of immune cell – that are wrongly trained to target the insulin-producing beta cells. When these wrongly trained T cells slip through the immune system’s checks, they can go on to destroy the beta cells.
The team wanted to test whether exposing developing T cells to a form of insulin during their initial ‘training’ could lead the immune system to recognise and delete T cells that would otherwise attack beta cells, before they ended up in the bloodstream.
What did they do?
The team modified specific ‘trainer’ immune cells so that these ‘trainer’ cells could present proinsulin – a form of insulin – to developing T cells. The modified ‘trainer’ cells were transplanted into diabetic mice, along with a specific type of newly developing T cells known to attack beta cells.
Another group of diabetic mice were given just the T cells and no modified ‘trainer’ cells, for comparison. The team then studied the mice’s immune system behaviour to see if the immune system deleted the damaging T cells that would attack the beta cells.
What did they find?
The researchers found that in mice with the proinsulin-presenting ‘trainer’ cells, the immune system deleted most of the T cells that would attack beta cells, and any remaining T cells were inactivated. In mice that were given the T cells but not the modified ‘trainer’ cells however, the T cells were not deleted.
What does this mean for type 1 diabetes?
This research indicates that exposing developing T cells to proinsulin can lead to beta-cell attacking T cells being deleted in mice. Understanding this process in mice might give researchers clues as to how a similar approach could work in people to prevent type 1 diabetes. In the long-term, this could lead to preventative treatments to delete or retrain the T cells wrongly developed to attack beta cells.
What’s the next step?
The next step for the team will be to see if similar ‘re-training’ strategies would work for T cells that have already been trained and released into the bloodstream. This could be useful in stopping the autoimmune attack once it is already underway.
More about the researchers
Associate Professor Raymond Steptoe who led this research, is a past grant recipient from JDRF, and regularly collaborates on JDRF research. He leads the Tolerance and Autoimmunity Group at the University of Queensland Diamantina Institute.
Dr Emma Hamilton-Williams is a current JDRF Career Development Award recipient and is part of the first pilot year of the JDRF/Macquarie Group Foundation Future Research Leaders Program (FRLP). She is a Research Fellow at University of Queensland Diamantina Institute and is currently investigating immune mechanisms of T1D, including how the bacteria in the gut interacts with our genes to affect T1D risk. Keep an eye on our blog for an upcoming profile of Dr Hamilton-Williams as part of the FRLP.
As T1D is an autoimmune disease, we need to understand the immune processes that lead to development of T1D before we can prevent it. JDRF is supporting many projects in the area of immune therapies including the role of different proteins and immune cells. To see our current research projects in Australia, head to our website.