Autoimmunity: Why Good T Cells Go Bad
In type 1 diabetes, the human body turns on itself. The immune systems of people with type 1 diabetes start attacking insulin-producing beta cells, as though they were the bacteria and viruses the immune system is supposed to fight off.
Researchers at Joslin Diabetes Center are puzzling out what causes the immune system to turn on what it’s meant to protect. The lab of Tom Serwold, Ph.D. studies why T cells, the immune system warriors, mistake beta cells for the enemy.
To understand where things go wrong, first we have to understand what happens when things go right.
“You can think of T cells as sort of like policemen in that they constantly traffic throughout the body and they interact with lots of other cells and lots of other tissues and they’re actively searching out for cells that are infected with bacteria or viruses,” said Dr. Serwold. “And the way they do that is by scanning the surface of cells for virus or bacteria products.”
All cells, whether they are infected or not, recycle the proteins that they produce within their walls. They deposit bits of these proteins onto their cell surfaces—healthy cells display bits of normal body proteins, infected cells are covered with bits of viral or bacterial proteins . T cells are programmed to recognize these bits of foreign proteins and to attack the cells that are covered with them.
A mouse thymus under a microscope light.
“The analogy here is if everybody who owned a house in Boston had to display pieces of their trash on the surface of their house and the police could just drive down the street and they would be able to look at every house and they would know basically what was going on inside that house by the different sorts of items that were displayed,” said Dr. Serwold. “For example, milk cartons, they would know the people were drinking a lot of milk, or if it was bullets, then they would know those people had been shooting bullets in their house.”
T cells learn which proteins signify an infection and which are the body’s own proteins in a small organ called the thymus, which is found behind the breastbone and above the heart. They get taught by cells residing in the thymus, known as thymic epithelial cells. These teacher cells produce proteins in the thymus that the T cells might encounter throughout the body, such as the proteins that help the body function normally, including insulin. T cells that are activated to attack by proteins like insulin get eliminated in the thymus, and only T cells that are non-reactive to the bodies own proteins are allowed to migrate out of the thymus and begin patrolling the tissues.
But in people with type 1 diabetes, something in this process goes wrong. Somehow, the T cells that can attack insulin-producing cells get released into the body to wreak havoc on the beta cells.
“So what we think is happening in type 1 diabetes, and in other autoimmune syndromes, is there is an incomplete or sort of a failure of the process of getting rid of those T cells that are capable of reacting to the body’s own cells,” said Dr. Serwold.
The Serwold lab is trying to find the fault in T cell development that allows for the bad T cell release. They are studying the makeup of the dysfunctional T cells to see where the education went wrong, and they are also looking into strengthening the education provided by the teacher cells.
A researcher takes sections of a thymus to study in depth.
Since the beta cells of people with type 1 diabetes have already been mostly destroyed, any autoimmune therapies derived from this research would only address half the problem. But for people who have a genetic risk for diabetes and show some autoimmune activity, catching defective T cells and improving education in the thymus could prevent the disease from ever occurring.
And for people who already have type 1, immune cell therapy could be coupled with the transplantation of beta cells, to both halt the autoimmunity and replace the damaged beta cells with functional ones.
“What my lab is working on is to prevent the autoimmunity,” said Dr. Serwold. “And so that’s one wing. And we think that’s going to be highly complementary to the other wing, which is the beta cell replacement. But it’s going to take both.”
Page last updated: February 21, 2019