Immune cells that may help sustain type 1 diabetes attack identified

Type 1 diabetes isn’t an overnight attack against the body’s ability to make insulin. It can be a sustained campaign over years that relentlessly targets insulin-producing cells in the pancreas. Scientists have not fully understood why this autoimmune attack—when the body’s immune system mistakenly destroys its own healthy cells—persists so long rather than petering out.

“People can generate autoimmunity occasionally, but it tends to be corralled by the body’s protective mechanisms,” said Todd Brusko, Ph.D., director of the University of Florida Diabetes Institute.

Brusko and a team of UF Health collaborators describe in a new study how a group of immune stem-like cells appears to perpetuate type 1 diabetes by potentially renewing themselves and replenishing the supply of immune T cells that carry out the autoimmune attack.

The study, relying on analysis of individual immune cells observed in unprecedented detail, was published in the Journal of Clinical Investigation. Leeana Peters, Ph.D., a postdoctoral fellow in Brusko’s lab, is the paper’s lead author.

“We confirmed something that had never really been described in human pancreas-draining lymph nodes,” said Brusko, the study’s senior author and a professor in the UF College of Medicine’s Department of Pathology, Immunology and Laboratory Medicine.

“Namely, that a population of stem-like T cells has this proliferative capacity. I think that is what is perpetuating autoimmunity as a chronic condition. These T cells likely persist and continue to drive the autoimmune attack for years or even decades.”

This is the first time this process has been described in human pancreatic lymph node tissues, Brusko said.

Tracing the immune cell lineage

All blood and immune cells begin as stem cells in the bone marrow. Some mature into lymphocytes, a type of white blood cell. Certain lymphocytes then develop into T cells.

Researchers analyzed pancreatic tissue and nearby lymph nodes from people with and without type 1 diabetes using advanced single-cell gene sequencing.

The technique lets scientists identify which genes were turned on, or expressed, in each cell and pinpoint molecular markers on the cell’s surface, helping them map the types of immune cells involved in the disease and how those cells might sustain the attack.

It’s akin to taking a photo of a busy intersection at different points in time to see who is coming and going and what kind of car they’re driving.

Knowing how the autoimmune attack unfolds in such detail could help researchers identify targets for new drug therapies to disrupt the disease.

Donor tissue expands the view

The study is one of a series of recent investigations by UF Diabetes Institute scientists using advances in technology and techniques to peer into the pancreas with a level of detail that was impossible even a decade ago.

This and other studies were made possible by the UF-based Network for Pancreatic Organ Donors with Diabetes, or nPOD, the world’s largest repository of donor pancreatic tissue. nPOD is a resource for scientists worldwide.

Historically, scientists studying type 1 diabetes largely relied on blood samples because pancreatic tissue is extremely difficult to obtain from living patients. nPOD tissue allows scientists to gain a clearer picture of the disease process, one that can only be obtained from donor tissue samples.

The work provides a list of potential targets at the site of the autoimmune attack that researchers believe might be vulnerable to new drugs.

“We think we can begin targeting these markers with therapeutic antibodies to halt the disease process,” Brusko said.