Fine-Tuning Cells to Tune Out Disease: Immune System Discoveries Spur Hope

To understand what causes type 1 diabetes (T1D), imagine a spy novel. It starts with a hero, the T-cell, that roams your body like James Bond. The T-cell hunts down enemies — bacteria and viruses — and snuffs them out. Then something goes terribly wrong: The hero becomes a villain.

Like a double agent, T-cells can turn against your body and attack your pancreas, triggering T1D. It keeps attacking for years, methodically destroying your ability to produce insulin and control blood sugar. Your T1D becomes ever more debilitating.

Fortunately, there’s hope: One of Benaroya Research Institute’s real-life heroes, Alice Long, PhD, is moving closer to a therapy that makes the enemy T-cells so exhausted they surrender.

alice-long1

BRI researcher Alice Long, PhD

“We think it could be possible to make the T-cells say ‘we give up, we’re too tired to keep attacking the pancreas,’” Dr. Long says. “That could slow down T1D or maybe even stop it.”

This approach of manipulating T-cells to stop disease could extend far beyond T1D. That’s why Dr. Long is teaming up with other BRI researchers, including BRI President Jane Buckner, MD, to study the machinery inside these cells more closely than ever before.

“This could reveal ways to dial T-cells down to stop autoimmune disease, or dial them up so they attack cancer,” Dr. Buckner says. “It’s a new frontier of immune research and BRI is excited to be at the forefront.” 

T-cell Discoveries

Dr. Long has dedicated her career to finding better therapies for the millions of people with T1D. The best available treatment is to inject insulin. Even then, T1D increases the risk of serious health issues like heart disease and stroke.

“There’s a desperate need for therapies that protect the pancreas so it can keep producing natural insulin, because that helps people with T1D stay healthier and have fewer complications,” Dr. Long says.

Dr. Long believes that understanding a phenomenon called “T-cell exhaustion” could unlock these therapies. Several years ago, researchers discovered the body is home to exhausted T-cells, which are alive but have stopped attacking. Everyone has these exhausted cells. But subsequent research showed that people with autoimmune disease who have higher numbers of these cells also have less severe disease and fewer complications. Then Dr. Long and Peter Linsley, PhD, made a key discovery of their own.

They showed that T1D progresses more slowly in people who have higher numbers of exhausted CD8 T-cells. They also found that a drug called teplizumab increased exhausted CD8 T-cells in most individuals. Even better, BRI researchers led a study that showed treatment with this drug delayed the onset of T1D by approximately three years in people who were susceptible to the disease.

“Those were ‘a-ha moments’ — we started to think, maybe it’s possible to create a therapy that exhausts these cells and stops T1D,” Dr. Long says. “But first we needed to understand these cells in much greater detail.”

Fine-Tuning the Immune System

Dr. Long recently received a $2.6 million National Institutes of Health grant to investigate why CD8 T-cells become exhausted and how this influences T1D. She’s also collaborating with Dr. Buckner and Erik Wambre, PhD, on an NIH-funded project that looks at T-cells in cancer patients.

People with cancer have the opposite problem as people with T1D and other autoimmune diseases. In cancer, T-cells should attack cancer cells, but something about cancer leaves them too exhausted to attack. Drugs called checkpoint inhibitors can nudge those cells back into attack mode. But those drugs can push T-cells into overdrive, until patients end up with symptoms similar to autoimmunity.

“If we can understand the process that leads to autoimmunity in these patients, it could help us understand the biological dial that controls how much T-cells attack,” Dr. Buckner says.

The BRI team’s vision is to be able to control both sides of the T-cell equation. This means they could adjust cancer therapies to prevent autoimmune attacks, or create therapies that exhaust attacker cells and stop autoimmune disease.

“We’re getting closer to being able to turn the immune system up or down depending on a patient’s needs,” Dr. Buckner says, “And that means we’re getting significantly closer to improving the lives of people with everything from T1D to cancer, and maybe even to stopping those diseases altogether.”


A version of this story originally appeared in the Benaroya Research Institute Autoimmune Life Blog

New Research Applies the Brakes to Type 1 Diabetes

A prevention study involving diabetes researchers and volunteers at Benaroya Research Institute at Virginia Mason (BRI) showed a drug that targets the immune system — Teplizumab — can delay type 1 diabetes up to three years in children and adults at high risk.

“This is great news for relatives of people with type 1 diabetes, who are at 15 times greater risk of the disease than the general population,” said Carla Greenbaum, MD, director of Interventional Immunology and the Diabetes Research Program at BRI.

Samples collected during the trial are being studied to help researchers understand why certain people responded to the drug better than others. Next, TrialNet researchers hope to conduct additional studies to look for ways to extend the benefits of the drug.

New Insight into Disease Progression

BRI Alice Long

BRI researcher Alice Long, PhD

When some people are diagnosed with type 1 diabetes, the disease progresses so quickly that their pancreas stops making insulin within a year. For others, the process is slower and their disease easier to manage. BRI research revealed that it’s possible to identify the “fast progressors” early and match them with treatments that help keep them healthy for longer.

BRI’s Alice Long, PhD, and her colleagues made the discovery that opened the door to potential new treatment strategies for type 1 diabetes. In a paper published in Journal of Clinical Investigation, the researchers identified important differences between fast progressors and people whose disease progresses much more slowly. Dr. Long’s team showed that slow progressors have higher levels of exhausted CD8 T cells — cells that are worn out from attacking the pancreas. The discovery could lead to a test that identifies how quickly individual patients will lose their ability to make insulin.

“Doctors may be able to give ‘fast progressors’ a therapy that’s going to slow down the attacker cells or maybe even stop them,” said Dr. Long, a BRI principal investigator. “For this group of people with type 1 diabetes, that would prolong their ability to make insulin, which makes their lives much easier and significantly reduces their long-term health risks.”


A version of this story originally appeared in the Virginia Mason Health System Annual Report. 

How Instagram – and Eating Vegan – Is Helping Create a Type 1 Diabetes Patient Community

In today’s socially connected world, people living with medical conditions don’t have far to look to find others sharing their experiences. These growing patient communities have given rise to thousands of websites, blogs, discussion and online groups – all with the goal of sharing ideas and understanding about managing, and even thriving, with medical diseases or disabilities. One unexpected patient online forum emerging today is within Instagram. How does an essentially visual medium create medical communities? I caught up with Michelle Peterson from t1dveganMama to learn how she’s using social media to connect with others who have type 1 diabetes.

What got you started posting on Instagram?

Initially I created an Instagram account to follow my friends’ activities. After a time I started following a few people living with type 1 diabetes (T1D.) I found their posts interesting because they were sharing information about the same things I was experiencing. It was actually my 14-year-old daughter’s idea to set up an Instagram account focused on living with T1D and eating a vegan diet.

What are some of the challenges living with type 1 diabetes?

I have had T1D for 46 years. It is a 24/7/365 disease. There are no breaks. You need to be pay attention to it constantly. While the technology for managing diabetes has improved tremendously over the years, you still need to make smart decisions about what you eat, when you eat, how much you exercise, when you exercise and how much insulin to take. You can do something one day and have beautiful, stable blood sugar levels, and do the exact same thing the next day and have blood sugar levels all over the place.

How long have you been a vegan?

Being vegan is fairly new to me. I tried it off and on in the past, but always missed cheese and seafood. About two months ago I transitioned to a totally vegan diet after my daughter began eating vegan. Now I’m not missing cheese or seafood! My husband has now started eating vegan too, but my two boys are not quite there yet.

Do you have some favorite vegan recipes?

I have found a lot of very good recipes on the Forks Over Knives website. White bean and avocado wraps are a favorite for my family. I also found a banana nut muffin recipe that is a hit.

white bean and avocado wrap

With the holidays coming, big meals and festive gatherings will abound. How do you manage these holiday meals – both as a vegan and a person with diabetes?

When I’m hosting, I don’t plan the entire meal around my diabetes. Nor do I plan to serve everything vegan. I serve a variety of options. I can eat anything; I just need to understand the impact of food on my blood sugar level. Many people think people with diabetes can’t eat sugar. That’s not true. I love this meme that says what people with diabetes can’t eat:

  1. Poison
  2. Cookies with poison

(diabetes humor)

What is your reaction to the growth of your Instagram following?

It’s rewarding. For me, having this network of people trying to manage diabetes well and stay healthy feels very supportive. People share some of the same thoughts about managing diabetes that I have. It’s validating. And, yes, I have T1Ds who are also vegans following me.

What advice do you have for people living with type 1 diabetes?

Make sure you have a good support system. It’s easy to feel alone and like no one understands what you are going through. Type 1 diabetes is often misunderstood, so educate people on what it is and what it isn’t. Be sure to align yourself with an excellent care team that you can reach out to when you need help with managing your diabetes. My last recommendation is that you don’t beat yourself up when your blood sugars are not doing what you want them to do. That’s going to happen, so focus on what you might do next to try to have the best control possible.

You can follow t1dveganmama too! Check out her tips for living with type 1 diabetes and a healthy vegan diet.

And don’t forget — Tuesday, Nov. 14 is World Diabetes Day. Learn more about type 1 diabetes from the American Diabetes Association and the JDRF TypeOneNation T1D support group.