Scientists create unique immune cells to protect transplants from attack

Scientists have developed immune cells for the first time that protect stem cell transplants from rejection by the body – and they could one day open the door to a cure for diabetes.

The new cells, which were able to protect insulin-producing cells transplanted into mice, were a first “proof of concept,” said the co-author of the study Audrey ParentAssociate Professor at the Diabetes Center at the University of California, San Francisco (UCSF).

However, if the designer cells prove safe and effective in humans, they could one day be used to protect transplanted tissue from attack, reducing or eliminating the need for drugs to suppress the tissue immune system. This, in turn, could pave the way to a cure for diseases like… Type 1 diabetes.

In type 1 diabetes, immune cells called killer T cells destroy the pancreatic beta cells that produce insulin. In recent years, scientists have come closer to replacing destroyed beta cells with new, stem cell-derived cells that can be transformed into any type of cell in the body.

Related: “Like a reset button on a computer”: Designer cells “reboot” the immune system in three different autoimmune diseases

In June, for example, the scientists turned around Type 1 diabetes in a person by reprogramming their fat cellswhile Boston-based Vertex Pharmaceuticals recently launched a pivotal, large-scale study Testing whether reprogrammed stem cells can eliminate the need for insulin in people with type 1 diabetes.

But before such stem cell transplants can be used across the board, scientists have to solve a big problem: In type 1 diabetes, killer T cells have been trained to attack beta cells and these cells have already been destroyed once. The transplanted cells need to be protected from this immune attack, so patients initially need strong drugs that suppress the immune system. However, these drugs make patients vulnerable to dangerous infections and are toxic to the kidneys and other organs.

To get around this problem, Parent and colleagues developed T cells in the laboratory that protected the transplanted cells – so-called transplants – from attacks.

“We took an immune cell and changed the machinery inside it to make it a protective cell instead of a killer cell,” Parent told Live Science. “And then we targeted it at the transplant.” Essentially, the designer cells act as bodyguards.

The bodyguards target beta cells because they recognize a specific protein called CD19 that the researchers added to the beta cells. When the bodyguard cells attack CD19, they produce a molecule that inhibits killer T cells.

The guards also make a protein that soaks up an inflammatory chemical that normally helps activate killer T cells. This anti-inflammatory protein also instructs the guards to replicate, creating a positive feedback loop that strengthens their ranks, Parent said.

To test their guardians in a living organism, the researchers then used beta cells derived from stem cells and implanted them into mice. They then sent killer T cells to attack the transplanted beta cells. They also injected a group of mice with their designer cells to defend the transplants.

In the mice that were not given designer cells, the killer cells quickly wiped out all the beta cells. But in the mice injected with designer cells, the transplants survived for at least 35 days and the mice were still producing insulin at that point, researchers reported in the study, published Thursday (Dec. 5) in the journal Science.

The results show that it is possible to engineer T cells that can protect transplanted tissue, Parent said.

A challenge, however, is finding a unique protein target to activate the designer cells, Parent said, since most potential targets on cells are found in multiple locations in the body. This increases the likelihood that their designer cells will be activated elsewhere in the body outside of the transplants. This could be a problem if, for example, cells become infected with the target protein or become cancerous but cannot be eliminated because they are protected by the guard cells. For such cases, transplanted cells could be engineered to have a “kill” switch, but other cells in the body would not have this switch.

Follow-up work could resolve this issue. For example, the team could develop an artificial target that would only be found on the transplanted beta cells and nowhere else, said the study’s co-author Wendell Lima biochemist and director of the UCSF Cell Design Institute, told Live Science in an email.

In a separate study also released Thursday ScienceLim and colleagues showed that similar designer T cells can attack brain tumor cells while leaving healthy brain cells alone. The cells could also deliver anti-inflammatory chemicals to brain cells of mice suffering from a disease similar to multiple sclerosis.

Looking forward, the team is also interested in seeing how this approach works against other autoimmune diseases triggered by inflammation, such as rheumatoid arthritis Crohn’s disease and other inflammatory bowel diseases, Lim added. But it will be several years before these ideas can be tested on humans, he said.

“This work opens a new avenue to target inflammatory diseases,” he said, “but many pieces need to be put together and tested to develop effective therapies.”

I ever wondered why Some people build muscle more easily than others or Why freckles appear in the sun? Send us your questions about how the human body works [email protected] with the subject line “Health Desk Q” and your question may be answered on the site!

Scientists create unique immune cells to protect transplants from attack

ByAmelia Journalton

By Amelia Journalton

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