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Australian scientists have made a discovery that may one day remove the need for a lifetime of toxic immunosuppressive drugs after organ transplants.

Researchers from the Garvan Institute of Medical Research have successfully tested a method of adjusting the immune system for just long enough to receive a tissue transplant and accept it as ‘self’. At no stage, during or after the procedure, is there any need for immunosuppressive drugs.

Lead by Professor Jonathon Sprent, the research team used a special immune boosting “complex” to successfully transplant islet cells into diabetic mice without the need of immunosuppression.

“Under normal circumstances, the body would attack a transplanted organ unless immunosuppressive drugs such as cyclosporin were given,” said Prof Sprent. “In this project, mice were given a substance, or ‘complex’, that altered their immune systems, so that they accepted transplanted cells as their own.”

This complex combines a molecule, interleukin-2 (IL-2), with an antibody. When given to the mice, this resulted in an increase in T-reg cells – the cells that quieten down the immune system, and a decrease in killer T cells – the cells that fight foreign materials.

The challenge for these researchers was that whilst this is the perfect situation for a tissue transplant, the lack of killer T cells means the body would be susceptible to attack from other areas such as infections or cancer cells. By changing testing different versions of the complex, they were able to suppress the immune system temporarily without risking infection.

According to research team member Stacy Walters, the results in mice were extremely encouraging.

“After treatment, the numbers of T regulatory cells dropped over time the immune systems returned to normal in about two weeks. By that time 80% of the mice had accepted the grafts of insulin producing cells as their own. A graft is considered accepted if it’s tolerated after 100 days. We took some mice out to 200-300 days, and not one of them rejected.”

While cautious, Professor Sprent is very encouraged by the results.

“We have yet to determine exactly how the complex works. Once we do, I believe a clinical trial of this very non-toxic agent would be worthwhile.”

“If we were able to duplicate this experiment in humans, it would fulfill the dream of everyone in the transplant field.”

Journal of Experimental Medicine pub online Feb 09

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