Scientists have unlocked the secrets of a little-understood immune cell, potentially paving the way for an easier way to treat and prevent graft-versus-host disease (GVHD).
GVHD occurs in up to 70 per cent of patients who receive a stem cell transplant to treat blood cancer. It is caused by donated immune cells (called T cells) attacking tissue in the recipient’s skin, gastrointestinal tract, liver or lungs. A significant proportion of patients who develop acute GVHD of the gastrointestinal tract do not survive.
QIMR Berghofer senior scientist Professor Geoff Hill, lead author Dr Ping Zhang, and their team have discovered that a type of T cell known as a type 1 regulatory T cell, or TR1 cell, plays a crucial role in fighting GVHD. Importantly, they have also discovered the protein that causes these cells to develop, allowing them to produce TR1 cells in large numbers in the laboratory.
The findings have been published today in the prestigious journal Science Immunology.
Professor Hill said that while conventional T cells fight disease and infection, regulatory T cells are responsible for keeping a check on immune responses and preventing them from causing harm.
“Regulatory T cells are particularly important for stem cell transplant recipients because they stop the donor cells from mounting an immune response against normal tissues,” Professor Hill said.
“There are two types of regulatory T cells: FoxP3 regulatory T cells, and TR1 cells.
“In most cases, FoxP3 regulatory T cells are more important and exist in much higher numbers than TR1 cells. But in this study, we found that TR1 cells are very important in stem cell transplantation.
“Patients with GVHD stop being able to make FoxP3 regulatory T cells and therefore have very low numbers of these cells. However, we found that when their levels decline, TR1 cells increase in number and become critical in stopping donor cells from attacking host tissues.
“In other words, TR1 cells compensate when FoxP3 regulatory T cells either fail or can’t be made.”
Dr Zhang said the researchers had also identified the particular protein that controls the development of TR1 cells.
“Knowing which protein controls the development of these cells means we can now find them easily in patients, and we’ve also been able to generate them in the laboratory,” he said.
Professor Hill said that it was also very exciting that the abundance of TR1 cells could be changed by specific signals delivered by molecules known as cytokines.
“It is probable that some of the therapies we are investigating in clinical trials induce TR1 T cells, and we are now able to examine this in our patients,” he said.
“Also, now that we understand more about how TR1 cells are produced and what they do, we hope to be able to generate them and give them to stem cell transplant patients to prevent GVHD.
“This is already being done with FoxP3 regulatory T cells, but we think it will be easier to do with TR1 cells.
“We hope that by giving patients infusions of these cells early on, we will eventually be able to prevent GVHD altogether.”
The study was funded by the National Health and Medical Research Council (NHMRC).