When some people are diagnosed with type 1 diabetes (T1D), the disease progresses so quickly that their pancreas stops making insulin within a year.  For others, the process is slower and this can make their T1D easier to manage.  But what if we could identify these fast progressors early, and match them with treatments that help them stay much healthier for much longer?

Alice Long, PhD, and her BRI colleagues have made a discovery that marks key progress towards this goal and opens the door to potential new treatment strategies. For example, her team found that slow progressors have higher levels of exhausted CD8 T cells — cells that are worn out from attacking the pancreas.

Their discoveries could lead to a test that helps doctors identify when someone’s T1D will progress quickly. And the study is already informing research into new potential treatments.

“We’re closer to being able to tell someone ‘you’re a fast progressor, and we can give you a treatment that’s going to slow down or stop the attacker cells,’” Dr. Long says.

Unprecedented Data

To study the differences between fast and slow progressors, Dr. Long’s team started by using tetramer technology as a molecular magnet to find the cells that cause T1D in each population.

“There are only about 1 of those cells in every 10,000 white blood cells,” Dr. Long says.

Then Peter Linsley, PhD, and BRI’s bioinformatics staff helped Dr. Long’s team analyze an unprecedented amount of data from these cells.  

“This research required a team of people who think about science in different ways — there’s no way we could have done this without everyone’s input,” Dr. Long says.

Exhausted Attackers

This teamwork enabled the researchers to identify higher numbers of exhausted CD8 T cells in slow progressors.

“These cells have been trying so hard to attack the pancreas that they get tired and say ‘nope, we’re not doing that today,’” Dr. Long says. “That means they leave the pancreas alone so it can function.”

Dr. Long envisions doctors someday using a test to determine how many exhausted CD8 T cells are in a T1D patient’s blood.

“If they don’t have many exhausted cells, the doctor could know they’re a fast progressor and put them on medication that preserves pancreas function for as long as possible,” she says.

Innovative Treatments

Dr. Long’s team also found that fast progressors have a higher number of activated memory cells — cells that have recently attacked insulin-producing beta cells in the pancreas.

“Next, we want to study these cells more closely and look for unique markers we could use to identify and target them,” Dr. Long says.

She and her colleagues are already investigating whether innovative therapies can cause more CD8 T cells to become exhausted.

“Those therapies might be able to slow T1D down in certain patients,” she says.

Dr. Long also recently received funding to investigate why these cells become exhausted in the first place.

“It could be possible to design treatments that go in and exhaust the cells,” she says. “They’d stop attacking the pancreas so people with T1D could live longer, healthier lives.”


Originally published in BRING IT ON newsletter - Winter 2020

Fighting Diseases

December 10, 2019

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