Signals Blog

Colourized scanning electron microscopy image of a T-cell. Image credit: National Institute of Allergy and Infectious Diseases.

Did you know that a healthy person with a healthy lifestyle and diet might still end up being diabetic? That is certainly the case with those who have type 1 diabetes (T1D). In T1D, the patient’s body has lost the ability to produce insulin. Insulin is a hormone that acts like an agent and takes care of moderating the amount of glucose (sugar) circulating in the body. Many years of research have shown that this loss is due to an autoimmune reaction. All of a sudden, a special group of the body’s immune cells, called the T-cells, start attacking the insulin producing cells of the pancreas, called the beta cells. The resulting lack of insulin causes an inability to control glucose levels in the blood and diabetes symptoms.

What is Autoimmunity?

When a foreign invader attacks the human body, our first line of defense is our immune system. The immune system is a complex network of cells, tissues, and organs that protect and defend our body against viruses, bacteria, fungi, and parasites. This amazing system gets trained in targeting agents of these enemies (substances called antigens) from the womb and after birth, and over time becomes more capable of stopping them by either secreting fluids that destroy the invaders or producing cells that can engulf and then destroy them.

The amazing thing about this system is that it is able to recognize and memorize many different enemies and, when healthy, can differentiate between normal body cells and tissue vs. invaders and their agents. However, in the large class of autoimmune diseases, the immune system loses this important quality and starts attacking the otherwise healthy body. Going rogue like this can result in immune cells attacking almost any part of the body.

This gives rise to complications associated with autoimmune disease, the most common of which is inflammation. Inflammation is due to increased immune cell activation in the tissue under attack. If the attack is on the joints, rheumatoid arthritis symptoms appear – such as stiffness, joint pain and loss of function. If it is on the central nervous system (brain, spinal cord, and optic nerves) symptoms of Multiple Sclerosis occur, which can range from double vision to difficulty in movements and eventually paralysis. If the immune cells attack the insulin producing cells in the pancreatic tissue, T1D happens. If you are interested, you can learn more about different autoimmune diseases here.

How does autoimmunity cause T1D?

Over the years, researchers have shown that in T1D there seems to be a complex interaction between two different types of immune cells called the B-cells and the T-cells. B-cells produce and secrete antibodies to a self-made insulin protein. Then, T-cells begin to destroy the pancreatic islets cells that produce that insulin, thus resulting in complete loss of function and ability to produce it further. The reactive B-cells are circulating in blood; however, the attacking T-cells remain in the tissue and are really hard to isolate and study.

Trapping the T-cells

Recently, a group of researchers at Harvard University (Harvard John A. Paulson School of Engineering and Applied Sciences(SEAS)),  Joslin Diabetes Center at Harvard Medical School and the Wyss Institute for Biologically Inspired Engineering has been able to create a biomaterial structure that could be used to capture and enrich the population of T-cells responsible for the destruction of the insulin producing cells of the pancreas.

The ingenious idea behind this study, published in the journal Diabetes, is that the researchers use an antigen-loaded biomaterial structure that looks similar to the insulin producing parts of the pancreas. This structure will recruit the self-destroying rogue T-cells that are sensitive to the known antigens. The T-cells increase in number inside this structure and can be isolated for further study. This way the researchers are able to monitor an ongoing T-cell mediated autoimmune attack and try to figure out the underlying reason that these cells become destructive. At the same time, they will be able to research immune-tolerance promoting drugs.

To test this, the researchers implanted a porous Poly (D,L- lactide-co-glycolide) (PLG) biomaterial scaffold that was loaded with ovalbumin and bits of insulin producing cells as antigens under the skin of non-obese diabetic (NOD) mice. These are mice with phenotypes similar to a person with T1D. After 14 days, the structures were taken out and the cells were isolated and further studied. A large population of T-cells had homed to the scaffold.

To make sure that they captured the cells responsible for diabetes, the researchers transferred these populations to mice that were genetically unable to produce T or B immune cells. Lo and behold, all the mice that received these cells became diabetic 10-20 weeks after the transfer. This proved that the researchers had captured the T-cells responsible for diabetes.

The next steps for such a study would be to test this scaffold in patients with T1D. So far, the scaffold has been shown to be safe and does not cause diabetes on its own. However, in order to be used in patients they need to make sure that all the antigens are completely bonded to the structure and T-cell enrichment is confined within its boarders.

The recruitment and enrichment of the diabetes-causing T-cells will help the researchers to isolate them and study an ongoing T-cell mediated autoimmune attack. They will be able to figure out the underlying reason that these cells become destructive and identify novel therapeutic approaches. Interestingly, such a structure can be used to study the behavior of T-cells in other types of autoimmune diseases such as Multiple Sclerosis and even cancer.

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Hamideh Emrani

Hamideh Emrani

Hamideh is a scientific communicator and the founder of Emrani Communications, serving clients in Toronto (University of Toronto) and California (Stanford University). She earned her B.Sc. in Cell and Molecular Biology at UC Berkeley and finished her M.Sc. at the University of Toronto (U of T). She was an intern at the Carnegie Institute at Stanford University, honours research student at UC Berkeley and has won awards for best podium and best poster presentations at the Faculty of Dentistry and IBBME at U of T. She is passionate about science and loves to talk and write about it. You can follow Hamideh on Twitter at @HamidehEmrani.