September 18, 2024
by Cardiff University
Graphical abstract. Credit: Journal of Clinical Investigation (2024). DOI: 10.1172/JCI164535
For the first time, scientists have found that proteins from bacteria can trigger the immune system to attack insulin-producing cells, leading to the development of type 1 diabetes.
The new research showed that killer T-cells—a type of white blood cell that’s involved in tackling bacterial infections—can cause type 1 diabetes when activated by bacteria. The researchers showed that proteins from bacterial species known to infect humans could generate killer T-cells that could kill insulin-producing cells.
This research, led by Professor Andrew Sewell at Cardiff University’s School of Medicine, expands on their previous studies, which demonstrated that killer T-cells play a major role in initiating type 1 diabetes by killing insulin-producing cells.
Professor Sewell said, “Type 1 diabetes is an autoimmune disease that usually affects children and young adults, where the cells that produce insulin are attacked by the patient’s own immune system. This leads to a lack of insulin, meaning that people living with type 1 diabetes need to inject insulin multiple times a day to control their blood sugar levels.
“There is currently no cure for type 1 diabetes and patients require life-long treatment. People living with type 1 diabetes may also develop medical complications later in life, so there is an urgent need to understand the underlying causes of the condition to help us find better treatments.”
In laboratory experiments, the researchers introduced bacterial proteins into cell lines from healthy donors and monitored the reaction of killer T-cells from these donors. They found that strong interaction with the bacterial proteins triggered killer T-cells to attack cells that make insulin.
The clinical lead for this study, Dr. Lucy Jones, said, “We observed this in relation to a specific HLA—human leukocyte antigen—a gene that codes for proteins that help the immune system differentiate between our own cells and invading cells.
“The specific HLA associated with the bacterial infection that triggers diabetes is only present in around 3% of the population in the UK. So the bacterial pathogens that can generate anti-insulin T-cells are caused by a rare infection in a small minority of people.”
Professor Sewell added, “Killer T-cells are able to target and attack body cells that produce a specific protein. We found that after encountering proteins from some infectious bacteria, killer T-cells could mistakenly also kill cells producing the insulin protein. We found activated T-cells with this same ‘cross-reactivity’ in the blood of patients with type 1 diabetes suggesting that what we saw in laboratory experiments could have triggered the disease.”
The research, published in the Journal of Clinical Investigation, provides the first evidence of how proteins from bacterial germs can trigger the type of killer T-cells seen in patients with type 1 diabetes. The team hopes that knowing more about this process, will allow new ways to diagnose, prevent, or even halt the development of type 1 diabetes.
“We hope that understanding how T-cells trigger diseases like type 1 diabetes will allow us to diagnose and treat disease before the onset of symptoms. Early treatment is known to result in a better prognosis as the healthy pancreatic beta cells that are being attacked can be protected before they are destroyed,” said Garry Dolton, the study’s first author.
Dr. Lucy Jones said, “Thanks to patients and health care staff being research active, this strong research collaboration between Cwm Taf Morgannwg University health board and Cardiff University has improved our understanding of diabetes.”
More information: Garry Dolton et al, HLA A*24:02–restricted T cell receptors cross-recognize bacterial and preproinsulin peptides in type 1 diabetes, Journal of Clinical Investigation (2024). DOI: 10.1172/JCI164535
Journal information: Journal of Clinical Investigation
Provided by Cardiff University
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