Transplant rejection – sometimes more is less

Most transplants need immunosuppressive drugs but livers often don’t . Why and how can we use this knowledge?

Could organs be transplanted without drugs?

New research may open the way to improved outcomes in organ transplantation. In animals, livers can be transplanted without immunosuppressive drugs. Dr Alexandra Sharland’s research explains this suprising result and suggests that use of drugs may actually reduce the chance of the transplant taking.

Dr Sharland, a postgraduate student at the Centenary Institute/Royal Prince Alfred Hospital in Sydney presented her results at ScienceNOW! the National Science Forum in Melbourne today.

“Organ transplants save the lives of thousands of Australians each year. Organs transplanted between unrelated individuals are always rejected unless immunosuppressive drug therapies are used to prevent rejection,” said Dr Sharland.

“However the drugs can have serious side effects, and despite their use, more than half of all transplanted organs are eventually rejected,” she said, “the challenge is to re-train the immune system so not to reject the foreign organ, while also maintaining normal immune protection against disease. ”

“Our research shows that when a liver is transplanted it causes a strong immune response in the recipient. Surprisingly this results in liver survival not rejection and suggests we should re-evaluate the present means of suppressing the immune system. ”

In a number of animal species, liver transplants have been accepted without the need for drug therapies. Dr Sharland’s work, as part a team of researchers, has shown that tolerance in liver transplants is associated with a stronger stimulation of the recipients’ immune system than is the case in skin or kidney transplants. The “over stimulation” results in cells from the recipients’ immune system becoming exhausted and dying, which has in turn prevented them from rejecting the liver. These studies also found that some drug therapies used to prevent rejection, may prevent this cell exhaustion and death, and so block tolerance.

The group’s current work aims to achieve tolerance to other organs such as kidney and heart by increasing the amount of immune stimulation provided by these organs at the time of transplantation.

The work for Dr Sharland’s Ph.D. was carried out under the direction of Dr Alex Bishop at the Centenary Institute/Royal Prince Alfred Hospital and in association with the Department of Transplant Surgery at Sydney University. The Centenary Institute is one of Australia’s leading medical research centres working in conjunction with Royal Prince Alfred Hospital in Sydney, specialising in transplantation and the diagnosis, prevention and treatment of many other diseases for example cancer, diabetes and asthma.

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