Breakthrough in transplant medicine

Apr 8 2009

Australian scientists have made a breakthrough in transplantation immunity by finding a way of stopping the immune system from rejecting transplanted organs.

A team of scientists at the Garvan Institute of Medical Research in Sydney have found a way of manipulating the immune system which could in future remove the need for the lifetime of toxic immunosuppressive drugs needed after organ transplants are carried out - the medications can increase the risk of infection and cancer but are presently vital in preventing the body rejecting an organ transplant.

The new treatment boosts the immune system prior to transplantation and was pioneered by Professor Jonathon Sprent, Professor Charles Surh from California's Scripps Research Institute and Dr. Onur Boyman, physician and Head of the Basic Immunology Unit at the University Hospital of Lausanne in Switzerland.

Professor Sprent says under normal circumstances, the body would attack a transplanted organ unless immunosuppressive drugs such as cyclosporin were given - in this new research mice were given a substance, or 'complex', that altered their immune systems, so that they accepted transplanted cells as their own.

After one month, not a single organ was rejected and after two weeks the immune system switched itself back on, and the organs were not rejected.

The complex combines a molecule, interleukin-2 (IL-2), with an antibody which together stimulate immune cells known as T regulatory cells and in simple terms provides a growth factor for T cells.

Dr. Boyman discovered that by combining IL-2 with different antibodies it's action can be controlled and specific populations of T cells boosted, while others are subdued.

Professor Sprent says T regulatory cells calm the immune system and subdue the body's killer T cells when it's time to stop fighting an infection; a superabundance of T regulatory cells prevents killer T cells from functioning but killer T cells are vital in fighting infections and cancers.

Dr. Sprent believes the treatment might be very useful for preventing rejection.

The experiment involved the research team injecting the complex into normal, healthy mice, for three consecutive days - on the fourth day insulin-producing cells were then transplanted - by this time large numbers of T regulatory cells were present in their systems, making the graft-destroying T cells ineffective.

The numbers of T regulatory cells decreased over time and the mice's immune systems returned to normal in about two weeks - 80% of the mice had by then accepted the grafts of insulin producing cells as their own.

Professor Sprent is cautious but very encouraged by the results and he says this level of acceptance rate is very high for transplantation, as mice normally reject grafts within 2-3 weeks - he says a graft is considered accepted if it's tolerated after 100 days and after 200-300 days not one of them rejected.

Professor Sprent believes the next step will be a clinical trial of the very non-toxic agent if they were able to duplicate the results in humans, it would 'fulfil the dream of everyone in the transplant field'.

The Garvan Institute of Medical Research is one of Australia's largest medical research institutions with nearly 500 scientists, students and support staff - main research programs are: Cancer, Diabetes & Obesity, Immunology and Inflammation, Osteoporosis and Bone Biology, and Neuroscience.

The research is published online in the current edition of the Journal of Experimental Medicine.