Immune attack: Artist's illustration of a white blood cell floating in the bloodstream among red blood cells. White blood cells such as T-cells are involved in the rejection of transplanted organs, but the discovery of a new hormone may lead to treatments that holds them at bay.
Credit: iStockphoto
BRISBANE: A hormone called BAFF can be used to prevent the body from rejecting a transplanted organ without the need for immunosuppressive drugs, researchers have found.
A new study, reported in the Journal of Immunology, shows that in mice a molecule called BAFF, or B-cell activating factor, sets off a chain of events in the immune system and prevents it from rejecting a transplant.
"We can manipulate the immune system to have immunosuppression-free transplants," said team leader and immunologist Shane Grey.
Serious side-effects
The immune system normally recognises that a transplant isn't part of the body and will quickly reject it unless strong immunosuppressive drugs are used. However, these drugs leave patients vulnerable to infections, cancer and kidney damage.
Even with immunosuppressants, the immune system can gradually destroy transplanted organs by hardening the blood vessels feeding them. Approximately 10 per cent of kidney transplants, for example, are rejected within five years.
The new research offers hope that the immune system can be manipulated more selectively to avoid the side effects of immunosuppressant drugs and prevent chronic immune attacks on transplanted organs.
Grey's team, at the Garvan Institute of Medical Research in Sydney, Australia, originally began investigating BAFF because they thought it might have a role in transplant rejection.
Because BAFF has been implicated in autoimmune diseases, such as rheumatoid arthritis, it was thought to be an inflammatory hormone, but the new study has shown that under certain circumstances it acts as an anti-inflammatory instead.
Identifying drug targets
Grey's team used mice genetically engineered to produce high levels of BAFF, and gave them transplants of islet cells, the insulin-producing cells of the pancreas.
Mice with normal BAFF levels rejected the transplants within 25 days, but 60 per cent of the high-BAFF mice still had healthy transplants after 100 days.
The high levels of BAFF increased the number of B-cells, which usually produce antibodies and were not thought to have a role in transplant rejection. However, the researchers found that the B-cells then caused an increase in the number of regulatory T-cells, which in turn control the activity of killer T-cells, which work to destroy transplants.
BAFF itself is currently too much of a "blunt instrument" to tackle transplant rejection in humans, Grey said, but his team plans to investigate the metabolic chain of events that allows BAFF to regulate T-cells, hoping to identify specific drug targets for human treatments.
Stephen Alexander, a paediatric transplant physician at the Children's Hospital at Westmead in Sydney, said that it was a very important finding. "They've identified a key signal that controls regulatory T-cells," he said. "BAFF clearly appears to be an important molecule in transplant immunology."
